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At least 55 records · Page 3Linked to original sources
PubMed2001

Elevated leukaemia inhibitory factor (LIF) expression in lesional psoriatic skin: correlation with interleukin (IL)-8 expression.

Psoriasis is a disease marked by keratinocyte hyperproliferation, neutrophil and lymphocyte infiltration, and aberrant epidermal and dermal expression of cytokines. Previously, it has been shown that LIF appears to be involved in skin inflammation and can induce the expression of IL-8. We sought to determine whether expression of LIF is abnormal in lesional psoriatic skin and whether this correlates with the expression of IL-8. Using reverse transcription polymerase chain reaction, we measured the expression of LIF and IL-8 mRNA in biopsies from normal individuals, non-lesional psoriatic skin, and lesional psoriatic skin. No difference was seen between the expression of IL-8 and LIF in normal and in non-lesional psoriatic skin. However, LIF expression in lesional skin was increased 160% compared with normal biopsies or non-lesional skin (p < 0.001). Immunostaining of frozen sections showed that the expression of LIF protein was principally suprabasal and, in the majority of sections, concentrated mainly in the stratum corneum of the lesional skin, whereas it was mainly in the stratum spinosum of the normal/non-lesional skin. IL-8 mRNA expression did not differ between the non-lesional and normal skin, but expression in the lesional skin was 17.6-fold greater than in normal skin (p < 0.001), and this expression was correlated with the increased LIF expression (r = 0.67, p < 0.001). Although a significant negative correlation was demonstrated between LIF mRNA expression and the duration of the last outbreak of the disease, no other correlations were found between levels of cytokine expression and a variety of parameters including PASI score. These data suggest a role for keratinocyte LIF in the psoriatic lesion and a link between LIF and IL-8 expression.

Adult↗
PubMed1986

Enhanced expression of c-myc and decreased expression of c-fos protooncogenes in chemically and radiation-transformed C3H/10T1/2 Cl 8 mouse embryo cell lines.

c-abl, c-fos, c-Ha-ras, c-myc, and c-mos were expressed whereas c-sis, c-fms, c-rel, c-src, and c-myb expression was not detectable in C3H/10T1/2 Cl 8 (10T1/2) cells and in eight chemically and radiation-transformed 10T1/2 cell lines. The expression of c-abl, c-fos, c-Ha-ras, and c-myc was growth-related in nontransformed 10T1/2 cells. c-abl and c-fos expression increased at confluence by 5- and 9-fold, respectively, compared to that in log phase cells. c-Ha-ras and c-myc transcripts were most abundant in log phase cells and decreased by 70 and 50%, respectively, in confluent cells. There were no significant growth-related changes in the expression of c-Ha-ras, c-myc, or c-abl in methylcholanthrene-transformed Cl 15 cells. The c-fos transcript was not detected in Cl 15 cell cultures. c-abl, c-fos, c-ras, and c-myc were expressed in whole C3H mouse embryo tissue, mouse liver, and 10T1/2 cells. Sizes of these protooncogene transcripts in 10T1/2 cells were the same as those in whole embryo tissue, except that 10T1/2 cells did not express the 8.2-kilobase abl transcript. At subconfluence, equivalent low levels of c-mos expression were observed in nontransformed and in the eight transformed 10T1/2 cell lines. The level of c-abl expression was similar in the nontransformed and in the eight transformed cell lines, but there was a new 8.2-kilobase transcript in the transformed MCA Cl 15 cell line. c-fos was expressed in 10T1/2 cells but was not detectable or greatly reduced in eight transformed cell lines. c-Ha-ras was expressed to a similar extent in eight transformed cell lines and in nontransformed 10T1/2 cells. In the UVC-4 transformed cell line, extra 3.3-kilobase Ha-ras and 7.5-kilobase Ki-ras transcripts were observed. c-myc was expressed at 4- to 7-fold higher levels in six transformed cell lines compared to 10T1/2 cells. There were no major rearrangements in or amplification of the c-myc gene in three transformed cells overexpressing this gene 5-fold. These studies show that enhanced expression of c-myc and decreased expression of c-fos correlate with the chemically and radiation transformed states of 10T1/2 cells. Changes in c-fos and c-myc oncogene expression may be casually linked to late stages of neoplastic transformation in these chemically and radiation transformed 10T1/2 cell lines.

Animals↗
PubMed1986

Differential expression of HLA class II antigens in fetal human spleen: relationship of HLA-DP, DQ, and DR to immunoglobulin expression.

Frozen sections of human fetal spleen from 12 to 20 wk gestation were examined by using polyclonal antibodies to Ig isotypes, monoclonal antibodies to HLA class II subregion locus products, B and T cells, and follicular dendritic cells. Scattered lymphoid cells in spleen sections from fetuses of 12 to 13 wk gestational age expressed IgM but not IgD. The appearance of lymphoid cells expressing IgD occurred at 14 to 15 wk before the formation of loose clusters of B cells at 16 wk. IgD expression was associated mainly with cells in these clusters, which by 17 wk had become definite follicles. Follicular dendritic cells were not detectable until 20 wk. OKT3-positive T cells were not detected until 17 wk, and at 20 wk constituted 5% of the nucleated cell population. HLA-DR- and DP-positive lymphocytes and macrophages were detectable in fetal spleen from 12 wk onward; DR was expressed on more cells than DP, and the numbers of cells stained by HLA-DR-specific monoclonal antibodies exceeded the number of Ig-positive cells in all spleens examined. HLA-DQ was expressed by consistently fewer cells than HLA-DR and -DP in all spleens tested. The small number of DQ-positive cells in spleens from 12- to 13-wk fetuses had the morphology of macrophages; HLA-DQ expression by lymphoid cells followed a similar pattern to IgD expression and was associated mainly with follicular lymphocytes. It could be demonstrated by double-labeling experiments that all follicular IgM-positive cells in 17- to 20-wk spleens expressed HLA-DP, DQ, and DR antigens: IgM-positive cells in 12- to 16-wk spleens and interfollicular IgM-positive cells in 17- to 20-wk spleens all expressed HLA-DR, but only 59% and 43% expressed DP and DQ, respectively. Ninety-one to 100% of IgD-positive cells in all spleens examined expressed HLA-DQ in addition to DR and DP. In these experiments IgD-negative, DQ-positive cells had the morphologic appearance characteristic of macrophages. These data suggest that class II antigens are differentially expressed on developing lymphoid cells; DR and DP expression occurring in the earliest spleens examined, with expression of DP on a subpopulation of DR-positive cells; IgD and DQ expression appears to be coincident on maturing B cells as they begin to form follicles. An immunoregulatory role for HLA-DQ in B cell development is implicated and remains to be fully investigated.

Antibodies, Monoclonal↗
PubMed2000

Expression of E-cadherin reduces bcl-2 expression and increases sensitivity to etoposide-induced apoptosis.

Expression of Bcl-2 is important in determining cancer cell resistance to chemotherapy. However, it is not clear whether cell-cell interactions regulate Bcl-2 expression. Using rat breast carcinoma cells selected for loss of hormone responsiveness, we found that parental E-cadherin-expressing cells (E cells) were more sensitive to etoposide-induced apoptosis than hormone-non-responsive cells (F cells), which failed to express E-cadherin. Expression of beta-catenin and pp120 src substrate proteins, which associate with E-cadherin, was unaffected. To determine whether re-expression of E-cadherin in F cells would restore etoposide sensitivity, F cells were transfected with an expression vector coding for the mouse E-cadherin gene. Stable clonal isolates expressing E-cadherin (F. Cad) showed increased sensitivity to etoposide treatment compared with control clones (F.Neo). Expression of E-cadherin resulted in a redistribution of beta-catenin from the cytoskeletal/nuclear fraction to the cytoplasmic/membrane fraction of the cells. E-cadherin-expressing clones also showed reduced invasion through basement membrane. Etoposide-induced apoptosis was characterized by morphological changes (nuclear blebbing) and DNA fragmentation. Induction of CPP32-like caspase activity was also observed in F.Cad transfectants but not F.Neo cells. Unlike F cells, F.Cad transfectants were not able to express Bcl-2, but transient transfection of bcl-2 resulted in re-expression and resistance to etoposide treatment. Therefore, E-cadherin may negatively regulate Bcl-2 expression by altering the availability of nuclear beta-catenin. Loss of E-cadherin in invasive tumor cells may lead to increased Bcl-2 expression and resistance to chemotherapeutic drugs.

Animals↗
PubMed2001

Chick CFC controls Lefty1 expression in the embryonic midline and nodal expression in the lateral plate.

Members of the EGF-CFC family of proteins have recently been implicated as essential cofactors for Nodal signaling. Here we report the isolation of chick CFC and describe its expression pattern, which appears to be similar to Cfc1 in mouse. During early gastrulation, chick CFC was asymmetrically expressed on the left side of Hensen's node as well as in the emerging notochord, prechordal plate, and lateral plate mesoderm. Subsequently, its expression became confined to the heart fields, notochord, and posterior mesoderm. Implantation experiments suggest that chick CFC expression in the lateral plate mesoderm is dependent on BMP signaling, while in the midline its expression depends on an Activin-like signal. The asymmetric expression domain within Hensen's node was not affected by application of FGF8, Noggin, or Shh antibody. Implantation of cells expressing human or mouse CFC2, or chick CFC on the right side of Hensen's node randomized heart looping without affecting expression of genes involved in left-right axis formation, including SnR, Nodal, Car, or Pitx2. Application of antisense oligodeoxynucleotides to the midline of Hamburger-Hamilton stage 4-5 embryos also randomized heart looping, but in contrast to the overexpression experiments, antisense oligodeoxynucleotide treatment resulted in bilateral expression of Nodal, Car, Pitx2, and NKX3.2, whereas Lefty1 expression in the midline was transiently lost. Application of the antisense oligodeoxynucleotides to the lateral plate mesoderm abolished Nodal expression. Thus, chick CFC seems to have a dual function in left-right axis formation by maintaining Nodal expression in the lateral plate mesoderm and controlling expression of Lefty1 expression in the midline territory.

Animals↗
PubMed2000

Expression of insulin-like growth factor-I (IGF-I) and IGF-II in the avian brain: relationship of in situ hybridization patterns with IGF type 1 receptor expression.

Insulin-like growth factors (IGFs) are expressed in defined spatiotemporal patterns during the development of the mammalian central nervous system (CNS). Since IGF expression in avian species is less well documented, we studied here the expression of IGF-I and IGF-II during chicken CNS development, using in situ hybridization and reverse transcriptase-PCR, and compared the results with the expression of the IGF type 1 receptor (IGF-1R). IGF-II expression started early in embryonic life, shortly after the onset of IGF-1R expression. During organogenesis, IGF-II was strongly expressed in kidney, liver and gut primordia, in contrast with IGF-1R mRNA, which is highly enriched in proliferating neuroepithelia. During the second half of embryonic development, IGF-I and IGF-II had distinct expression patterns, suggesting specific roles for each ligand during brain maturation. IGF-II mRNA was found in numerous brainstem nuclei and in the optic tectum, whereas IGF-I mRNA was found predominantly in telencephalic regions. Both ligands were expressed in the cerebellum, but each by different cell layers. Some brain regions (olfactory bulb and olivo-cerebellar system) did not exhibit the postnatal downregulation typical of extrahepatic IGF-I expression, but continued to express IGF-I into adulthood. Purkinje cells expressed IGF-II in the embryo, but switched to IGF-I expression in the adult. The conservation of embryonic and postnatal IGF expression patterns in the CNS between avians and mammals suggests that the involvement of the IGF system in neurogenesis and differentiation, and possibly in neural plasticity and learning, may have arisen early during tetrapode/vertebrate evolution.

Age Factors↗
PubMed2000

Expression of oncogenic epidermal growth factor receptor family kinases induces paclitaxel resistance and alters beta-tubulin isotype expression.

Oncogenic transformation confers resistance to chemotherapy through a variety of mechanisms, including suppression of apoptosis, increased drug metabolism, and modification of target proteins. Oncogenic epidermal growth factor receptor family members, including EGFRvIII and HER2, are expressed in a broad spectrum of human malignancies. Cell lines transfected with EGFRvIII and HER2 are more resistant to paclitaxel-mediated cytotoxicity, and tubulin polymerization induced by paclitaxel is suppressed compared with cells expressing wild type epidermal growth factor receptor. Because differential expression of beta-tubulin isotypes has been proposed to modulate paclitaxel resistance, we analyzed beta-tubulin isotypes expressed in cell lines transfected with different oncogenes. EGFRvIII- and HER2-expressing cells demonstrated equivalent total beta-tubulin protein compared with cells transfected with wild type receptor or untransfected controls. EGFRvIII-expressing cells demonstrated increases in class IVa (2.5-fold) and IVb (3.1-fold) mRNA, and HER2-expressing cells showed increases in class IVa (2. 95-fold) mRNA. Expression of oncogenic Ha-Ras did not change class IV RNA levels significantly. Inhibition of EGFRvIII kinase activity using a mutant allele with an inactivating mutation in the kinase domain decreased expression of class IVa by 50% and partially reversed resistance to paclitaxel. Expression of oncogenic epidermal growth factor receptor family members is associated with modulation of both beta-tubulin isotype expression and paclitaxel resistance in cells transformed by expression of the receptor. This effect on tubulin expression may modulate drug resistance in human malignancies that express these oncogenes.

3T3 Cells↗
PubMed2000

A hormone response element in the human apolipoprotein CIII (ApoCIII) enhancer is essential for intestinal expression of the ApoA-I and ApoCIII genes and contributes to the hepatic expression of the two linked genes in transgenic mice.

We have generated transgenic mice carrying wild-type promoters of the human apolipoprotein A-I (apoA-I)-apoCIII gene cluster or promoters mutated in their hormone response elements. The wild-type cluster directed high levels of apoA-I gene expression in liver and intestine, moderate expression in kidney, and low to minimal expression in other tissues. It also directed high levels of chloramphenicol acetyltransferase (CAT) expression (used as a reporter for the apoCIII gene) in liver, low levels in intestine and kidney, and no expression in other tissues. Mutations in the apoCIII promoter and enhancer abolished the intestinal and renal expression of the apoA-I gene, reduced hepatic apoA-I expression by 80%, and abolished CAT expression in all tissues. A similar pattern of expression was obtained by mutations in the apoCIII enhancer alone. Mutations in the proximal apoA-I promoter reduced by 85% hepatic and intestinal apoA-I expression and did not affect CAT expression. The findings suggest that a hormone response element within the apoCIII enhancer is essential for intestinal and renal expression of apoA-I and apoCIII genes and also enhances hepatic expression. The hormone response elements of the proximal apoA-I promoter or the apoCIII enhancer can promote independently low levels of hepatic and intestinal expression of the apoA-I gene in vivo.

Animals↗
PubMed1999

Coordinated expression of noggin and bone morphogenetic proteins (BMPs) during early skeletogenesis and induction of noggin expression by BMP-7.

Coordinated regulation of the activities of bone morphogenetic protein (BMP) and its inhibitors is essential for skeletal development since loss-of-function experiments show that both BMPs and BMP inhibitory signals, such as noggin, are required to establish proper formation of skeletal tissues. In this paper, we asked how and when noggin would be functional to interact with BMPs during skeletogenesis in mammals. For this purpose, we first analyzed the spatial and temporal patterns of noggin, BMP-2, BMP-4, and BMP-7 expression during early skeletogenesis in mouse embryos. In situ hybridization study revealed that noggin expression was detected at a low level in limb mesenchyme, whereas BMP-7 was expressed at a high level throughout limb mesenchyme 10.5 days postcoitum (dpc) in mouse embryos. One day later, noggin mRNA was expressed at a high level in the prechondrogenic condensations in appendicular and axial skeletal primordia, where sox9 transcripts were also expressed. At this stage, noggin-expressing cells were surrounded by those expressing BMP-7. The chondrogenic cell condensation continued to express noggin transcripts in 12.5 dpc and 13.5 dpc embryos, and again the noggin-expressing cells within the cartilaginous tissue were surrounded by those expressing BMP-7. We further examined interaction of noggin and BMPs by using organ cultures of 11.5 dpc mouse forelimbs and found that implantation of carriers containing BMP-7 protein into the forelimb explants induced noggin expression in the limb mesenchyme. BMP-7 also induced type II collagen and sox9 mRNAs in the same cell population, indicating that noggin induction occurred in the chondrogenic precursor cells. BMP-7 effects on noggin expression were observed in a dose-dependent manner within a dose range of 10-100 ng/microliter. These results suggest that BMP-7 induced expression of noggin transcripts within skeletal cell condensation and that this noggin expression in turn could act antagonistically to attenuate BMP action in the early skeletogenesis.

Animals↗
PubMed1998

Differential expression of Wnt genes in normal and flat variants of PC12 cells, a cell line responsive to ectopic Wnt1 expression.

Wnt genes encode secreted growth factor-like proteins that participate in growth regulation, differentiation and tumorigenesis. Ectopic expression of Wnt1 converts the PC12 neural crest-derived rat pheochromocytoma cell line from a round phenotype that express chromaffin markers to flat adherent cells (termed PC12/Wnt1) that do not express them. A pool of spontaneously flat variants of PC12 cells (PC12/flat) is phenotypically similar to the PC12/Wnt1 cells, but does not express Wnt1. Here we describe the expression of 13 Wnt genes in wild type PC12, PC12/flat and PC12/Wnt1 cells. Wild type PC12 expressed Wnt3, Wnt3a, Wnt4, Wnt5a, Wnt6, Wnt10a and Wnt11. Compared with expression in wild type cells, both PC12/flat and PC12/Wnt1 cells lost most or all expression of Wnt3a and Wnt4 and gained expression of Wnt7b. Wnt5a and Wnt6 expression was higher in PC12/Wnt1 cells than in PC12 or PC12/flat. Wnt3 was expressed at low levels in both PC12 and PC12/flat, but was absent in PC12/Wnt1 cells. Wnt10a and Wnt11 were approximately equally expressed in the three groups, and Wnt2, Wnt5b, Wnt7a, Wnt10b and endogenous Wnt1 mRNAs were not detected. These results demonstrate that the expression of some Wnt genes changes in PC12 cells upon conversion to the flat phenotype, and suggest that Wnt1 may modulate expression of several other Wnt genes in these cells.

Animals↗
PubMed1997

Phenotypic characterization of neurotensin messenger RNA-expressing cells in the neuroleptic-treated rat striatum: a detailed cellular co-expression study.

The chemical phenotype of proneurotensin messenger RNA-expressing cells was determined in the acute haloperidol-treated rat striatum using a combination of (35S)-labelled and alkaline phosphatase-labelled oligonucleotides. Cellular sites of proneurotensin messenger RNA expression were visualized simultaneously on tissue sections processed to reveal cellular sites of preproenkephalin A messenger RNA or the dopamine and adenylate cyclase phosphoprotein-32, messenger RNA. The cellular co-expression of preproenkepahlin A (enkephalin) and preprotachykinin (substance P) messenger RNA was also examined within forebrain structures. Cellular sites of enkephalin (substance P) and dopamine and adenylate cyclase phosphoprotein-32 messenger RNAs were visualized using alkaline phosphatase-labelled oligonucleotides whilst sites of substance P and proneurotensin messenger RNA expression were detected using (35S)-labelled oligos. Cellular sites of enkephalin and dopamine and adenylate cyclase phosphoprotein-32 gene expression were identified microscopically by the concentration of purple alkaline phosphatase reaction product within the cell cytoplasm, whereas sites of substance P and proneurotensin gene expression were identified by the dense clustering of silver grains overlying cells. An intense hybridization signal was detected for all three neuropeptide messenger RNAs in the striatum, the nucleus accumbens and septum. Dopamine and adenylate cyclase phosphoprotein-32 messenger RNA was detected within the neostriatum but not within the septum. In all forebrain regions examined, with the exception of the islands of Calleja, the cellular expression of enkephalin messenger RNA and substance P messenger RNA was discordant; the two neuropeptide messenger RNAs were detected essentially in different cells, although in the striatum and nucleus accumbens occasional isolated cells were detected which contained both hybridization signals; dense clusters of silver grains overlay alkaline phosphatase-positive cells, demonstrating clearly that these dual-labelled cells expressed both messenger RNAs. By contrast, the hybridization signals for proneurotensin and enkephalin, and proneurotensin and dopamine and adenylate cyclase phosphoprotein-32 were generally coincident, at least within the neostriatum; most proneurotensin messenger RNA-positive cells expressed enkephalin messenger RNA and were also positive for dopamine and adenylate cyclase phosphoprotein-32 messenger RNA. However, occasional proneurotensin messenger RNA-positive striatal cells were identified that were single-labelled and did not express enkephalin messenger RNA. Within the septal nucleus, enkephalin messenger RNA and substance P messenger RNA were expressed essentially within segregated cell populations. These studies illustrate further the utility of co-expression techniques for investigating the chemical phenotype of cells within the CNS and demonstrate that the distribution of neuropeptide co-expressing cells is different within different brain regions. That several populations of proneurotensin messenger RNA-positive striatal cells may exist, of which one population is sensitive to haloperidol, co-expresses enkephalin messenger RNA and is positive for dopamine and adenylate cyclase phosphoprotein-32 messenger RNA may be of some significance in neuropsychiatric/neurological disorders given that the translated peptide, neurotensin, is known to influence and interact closely with the dopamine systems.

Animals↗
PubMed1996

Expression of receptors for epidermal growth factor and insulin-like growth factor I by ZR-75-1 human breast cancer cell variants is inversely related: the effect of steroid hormones on insulin-like growth factor I receptor expression.

We have investigated the expression of insulin-like growth factor I receptors (IGFR) by the ZR-75-1 human breast cancer cell line and tamoxifen-resistant (ZR-75-9a1) and oestrogen-independent (ZR-PR-LT) variants. ZR-75-1 cells expressed 6633+/-953 receptors per cell,(K(d) 0.24+/-0.06 nM). IGFR expression was reduced in ZR-75-9a1 cells (1180+/-614 receptors per cell, K(d) 0.13+/-0.05) and increased in the ZR-PR-LT cell line (18 430+/-3210 receptors per cell, K(d) 0.24+/-17). A comparison of these data with previously published findings for epidermal growth factor receptor (EGFR) expression by these cell lines revealed that IGFR and EGFR expression are inversely related in the variant lines whereas ZR-75-1 cells express similar numbers of both receptors. Since the changes in IGFR expression observed are associated with changes in steroid hormone receptor status, we also investigated the effects of oestradiol, the synthetic progestin ORG 2058 and dexamethasone on IGFR expression. Oestradiol increased IGFR expression only in the ZR-75-1 cell line. Low concentrations of ORG 2058 increased IGFR levels in the two cell lines positive for progesterone receptor (ZR-75-1 and ZR-PR-LT). High concentrations of ORG 2058 increased IGFR expression in all cell lines, as did dexamethasone. These data suggest that EGFR and IGFR expression may be linked in breast cancer, and that EGFR/IGFR ratios in breast cancer may be a more sensitive prognostic indicator than EGFR expression alone. Regardless of basal IGFR expression by the cell studied, ORG 2058 increased IGFR expression, possibly via both the progesterone and glucocorticoid receptors.

Breast Neoplasms↗
PubMed1992

Evidence by in situ hybridization that c-erbB-2 proto-oncogene expression is a marker of malignancy and is expressed in lung adenocarcinomas.

In order to identify potential markers of malignancy in diagnostic respiratory cytopathology, c-myc and c-erbB-2 proto-oncogene expression was studied in fine needle aspirates from 14 consecutive fresh operation tissue samples (after surgical removal) representing lung tumors and a variety of other cell samples by in situ hybridization of 35S-labeled antisense and sense RNA c-myc and c-erbB-2 specific proto-oncogene probes. All 14 lung tumors showed c-myc expression and eight also showed c-erbB-2 expression. On average, the c-myc expression was about 4 times higher than that of c-erbB-2 (P less than 0.001). c-erbB-2 expression, confirmed also as a cytoplasmic membrane-bound reactivity by immunohistochemical stainings for c-erbB-2 oncoprotein, was significantly related to adenocarcinoma (P less than 0.025), whereas increasing tumor size correlated significantly with increasing c-myc expression (P less than 0.05). On average, all the tumor cell lines showed 2-fold expression of c-myc compared with the lung tumors (P less than 0.025). c-erbB-2 expression was found in six of 11 cell lines. High c-myc proto-oncogene expression was also found in broncho-epithelial cells and alveolar macrophages, and a low expression was found in lymphocytes but not in neutrophils, while none of these cells showed c-erbB-2 proto-oncogene expression. Our results demonstrate extensive c-myc proto-oncogene expression in both malignant and non-neoplastic proliferating cells, but not in terminally differentiated cells such as neutrophils. Therefore c-myc expression must also be related to general cell proliferation and not only malignancy per se. In marked contrast, c-erbB-2 proto-oncogene expression was found only in adenocarcinoma cells, and thus can be used as a marker for malignancy in diagnostic respiratory cytopathology.

Adenocarcinoma↗
PubMed1987

Separate induction of MHC and thyroid microsomal antigen (McAg) expression on thyroid cell monolayers: enhancement of lectin-induced McAg expression by interferon-gamma.

Interferon-gamma (IFN gamma) induced the expression of the MHC class II antigens HLA-DR and -DQ on 1- to 2-week-old thyrocytes from normal thyroid tissue and thyroid tissue from patients with autoimmune thyroid disease; it also enhanced the expression of B2-microglobulin, which is associated with MHC class I molecules. However, the expression of thyroglobulin and thyroid microsomal antigen (McAg) was not detected after IFN gamma stimulation. Autologous and allogeneic peripheral blood mononuclear cells had the same ability as IFN gamma to induce antigen expression when cocultured with thyrocytes. In contrast, leucoagglutinin (LAG) induced McAg as well as HLA-DR and B2-microglobulin expression on thyrocytes, but not thyroglobulin expression. Concanavalin A and pokeweed mitogen also induced McAg expression. The time course of LAG induction of McAg was not always correlated with that of HLA-DR. Anti-IFN gamma, antiinterleukin-2 receptor, and anti-HLA-DR monoclonal antibodies inhibited LAG or peripheral blood mononuclear cell induction of HLA-DR expression, but not LAG induction of McAg expression. Anti-HLA-DR reduced the IFN gamma induction of HLA-DR. INF gamma enhanced thyrocyte McAg expression induced by LAG, especially when thyrocytes were incubated with IFN gamma for 24 h before LAG stimulation. In contrast, in the absence of LAG stimulation, IFN gamma suppressed already present spontaneous McAg expression. TSH did not induce McAg and HLA-DR expression on DR-negative thyrocytes, but enhanced weak DR expression induced by other stimulants, e.g. IFN gamma or lectins. These data suggest that in vitro induction mechanisms of MHC class I and II antigens and McAg are different; MHC antigens are induced by IFN gamma, whereas McAg is induced by lectin, probably acting on thyrocytes directly; and IFN gamma has an enhancing effect on LAG-induced thyrocyte McAg expression.

Antigens↗
PubMed1990

The regulation of expression of MHC products in mice. Factors determining the level of expression in kidneys of normal mice.

Cytokines, especially IFN, have been shown to increase MHC expression above basal levels in many immunologic processes, but their contribution to normal MHC expression is unknown. Environmental stimuli, such as bacterial LPS, may provoke the secretion of cytokines which could influence MHC expression in the normal host. We therefore studied the factors influencing the normal expression of MHC products in mice, by using kidney as a representative nonlymphoid tissue. Considerable variation in MHC expression was observed between otherwise normal individuals by using indirect immunoperoxidase staining and a radiolabeled antibody binding assay. An intact T cell compartment was not necessary for normal levels of expression; in athymic nude mice and mice with severe combined immunodeficiency disease, MHC expression was similar to or greater than that of controls. Neither a course of broad spectrum antibiotics nor genetically determined resistance to LPS influenced the level of normal expression. Mice raised under germ-free conditions, on a chemically defined diet also had similar levels of MHC expression when compared with mice maintained under conventional conditions. However, when germfree mice were placed in a conventional colony, induction of both class I and II MHC products occurred. Thus, although exposure to bacterial flora or other sources of endotoxin was not required for normal MHC expression, a change in flora can up-regulate expression, probably by inducing the secretion of cytokines from non-T cells. Treatment with cyclosporine or anti-IFN antibodies produced, at most, a small reduction in the level of renal MHC expression. Therefore in some mice, a small component of MHC expression may reflect the secretion of cytokines in response to stimuli such as bacterial LPS. However, most MHC expression in nonlymphoid tissues is constitutive and independent of a physiologic IFN response.

Animals↗
PubMed1998

Nuclear expression of YB-1 protein correlates with P-glycoprotein expression in human osteosarcoma.

The Y-box-binding protein, YB-1, is a member of the DNA-binding protein family. It binds to the Y-box, an inverted CCAAT box, in the promoter region of the human multidrug resistance 1 gene, which encodes P-glycoprotein (P-gp). Nuclear localization of YB-1 protein has been reported to be associated with the intrinsic expression of P-gp in human breast cancer. We studied the immunohistochemical expression of YB-1 protein in 69 untreated biopsy specimens of conventional osteosarcomas and compared it with the expression of P-gp. Furthermore, cell proliferation, as determined by the MIB-1-labeling index (MIB-1-LI), was measured by immunohistochemistry. In all 69 untreated osteosarcomas, YB-1 protein was expressed in the cytoplasm. In 32 of 69 (46%) cases, YB-1 was also localized in the nucleus. The expression of P-gp was evident in 23 of these 32 cases, and there was a significant correlation between the nuclear expression of YB-1 and P-gp expression (P < 0.0001). Chondroblastic osteosarcoma expressed YB-1 in the nucleus more frequently (eight of nine cases) than did other types of osteosarcoma, whereas P-gp was also frequently expressed in chondroblastic subtype. There was no correlation between the nuclear expression of YB-1 and histological grade. The MIB-1-LI was significantly higher in cases showing the nuclear expression of YB-1 (MIB-1-LI averaged 22.56 in cases with only cytoplasmic expression of YB-1 but averaged 28.20 in cases with cytoplasmic and nuclear expression of YB-1; P = 0.0477). In human osteosarcoma, nuclear localization of YB-1 protein was associated with the expression of P-gp, suggesting that YB-1 could be a prognostic marker for multidrug resistance in osteosarcoma.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

Platelet glycoprotein IIb gene expression as a model of megakaryocyte-specific expression.

Glycoprotein (GP)IIb/IIIa is an integrin complex normally restricted in its expression to platelets and the megakaryocytes from which they are derived. This complex functions as a receptor for fibrinogen and other ligands and is involved in platelet aggregation. The receptor complex is expressed at high levels during final megakaryocyte differentiation. Further, while GPIIIa is expressed in other tissues as part of the vitronectin receptor, GPIIb is only expressed on maturing megakaryocytes and the platelets derived from them. Thus studies of the GPIIb gene may serve as a model of gene regulation during this process. Over the past several years, the genes for both GPIIb and IIIa have been cloned and analyzed. The GPIIb gene contains 30 exons over 18 kilobases (kb). The transcriptional start site has been determined and there does not appear to be a TATA-box immediately upstream of this site. Studies have been done to define regulatory elements upstream of the transcriptional start site. Most of these studies focused on the human promoter and on studies using megakaryocytic cell lines. These studies have defined several important tissue-specific promoter elements including a GATA454 site (454 basepairs upstream of the transcriptional start site that involves a GATA-binding consensus sequence), a GATA54 site and an Ets35 site (that involves an Ets-binding consensus sequence). Expression studies with megakaryocytic cell lines suggest that each of these sites effects expression approximately threefold. Further, an Ets510 site was also described that had a similar effect. While these studies were underway, we pursued studies of the rat 5'-flanking region using a rat primary marrow expression system. Qualitatively, our data support the human data; however, quantitatively, we found significant differences from the human studies done in cell lines. We found that the major tissue-specific promoter element was the GATA454 site. Mutations altering this site result in an approximately fiftyfold drop in expression. In comparison, eliminating the Ets510 site by truncation or point mutation had only a twofold effect on expression. Mutations at the Ets35 site did effect expression at a high level, decreasing expression approximately fifteenfold, while mutations at the GATA54 site effected expression by approximately ninefold. In addition, using 50 bp deletions, we have preliminarily defined two domains from -450 to -351 bp and -150 to -101 bp upstream of the transcriptional start site that effected expression. The former appears to contain a positive regulatory element, while the latter appears to be a silencer element.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1995

Collagen gene expression during development of avian synovial joints: transient expression of types II and XI collagen genes in the joint capsule.

The developmental sequence of the embryonic joint has been well studied morphologically. There are, however, no definitive studies of cell function during joint development. In order to begin to understand the differentiation events that contribute to joint formation, we examined the expression of collagen mRNAs encoding types I, IIA, IIB, and XI. In situ hybridization was performed on chicken embryo hind limb buds and digits from day 7 to day 18 (Hamburger and Hamilton stages 31-44). In the day 7 (stage 31) limb bud, there was a condensation of mesenchyme forming the primitive tarsal and metatarsal bones that showed abundant expression of type IIA procollagen message, but no type IIB or type alpha 1(XI) message. By day 8 (stage 33), co-expression of types IIA, and type XI procollagen mRNAs was observed in the condensations, with expression of IIB restricted to early chondrocytes with metachromatically staining matrix. At this stage, DNA fragmentation characteristic of apoptosis was observed in cells near the midline of the interzone region between the developing anlagen, and in areas between and around the individual digits of the paddle. The presumptive apoptotic cells were more numerous at day 9 (stage 35), and were not found in the developing joint at subsequent time points, including the initiation of spatial cavitation of the joint. From days 11-18, type IIA procollagen mRNA was expressed in flattened cells at the surface of the anlagen, and in the perichondrium and in the developing joint capsule; type IIB mRNA message was found only in chondrocytes. Type XI mRNA was expressed by all type II-expressing cells. Alpha 1(I) mRNA was expressed early by cells of the interzone and capsule, but as cavitation progressed, the type I expressing cells of the interzone merged with the superficial layer of the articular surface. Thus, at the time of joint cavitation, there was a distinct pattern of expression of procollagen messages at the articular surface, with type I being outermost, followed by morphologically similar cells expressing type IIA, then chondrocytes expressing type IIB. The progenitor cells expressing type IIA message define a new population of cells. These cell populations contribute to the molecular heterogeneity of the articular cartilage, and these same populations likely exist in the developing joints of other species. The transient transcription of type II and type XI collagen genes, characteristic of chondrocytes, by cells in the joint capsule demonstrates that these cells may have chondrogenic potential.

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