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At least 667 records · Page 37Linked to original sources
PubMed1997

Tissue and differentiation specific expression on the endogenous retrovirus ERV3 (HERV-R) in normal human tissues and during induced monocytic differentiation in the U-937 cell line.

ERV3 (HERV-R) is a complete, single copy human endogenous retrovirus located on the long arm of chromosome 7. The open reading frame in its envelope gene has been conserved during evolution but the gag and pol genes contain in-frame termination codons. To find a suitable experimental model system for analysis of the functions of the ERV3 genome, an extensive screening study of different normal and neoplastic human tissues was performed. Most tissues express low levels of the ERV3 env mRNA although high expression levels are observed in placenta, sebaceous glands, adrenals, testis, bronchial, epithelium and the monocytic cell line U-937. In U-937 cells the ERV3 env expression varied in a manner related to the differentiation status of the cells; being highest in the terminally differentiated non proliferating cells. U-937 cells can be induced to differentiate from the monoblastic to the mature monocyte/macrophage stage upon stimulation by several substances such as phorbolesters (TPA), Vitamin D3, Retinoic Acid (RA) and combinations of some cytokines. We conclude that the ERV3 locus is expressed in a tissue and differentiation specific way and that the U-937 cell line is a suitable model system to further analyze the proposed functions of ERVs such as immunomodulation, cell fusion and protection against exogenous retroviral infections.

Cell Differentiation↗
PubMed1997

Differential expression of the regularly spliced wild-type p53 and its COOH-terminal alternatively spliced form during epidermal differentiation.

In the present study, we investigated the role of p53 in the differentiation of epidermal keratinocyte cells. The interrelationship between p53 expression and the various stages of epidermal differentiation and the role of the COOH terminus of the p53 molecule in this process were determined by comparing the expression of the regularly spliced p53 (RSp53) molecule and that of the COOH-terminal alternatively spliced (ASp53) form. p53 mRNA distribution was studied by in situ analysis of frozen skin sections and by reverse transcription-PCR analysis of the various wild-type p53 forms expressed in neonatal skin cell fractions separated by Percoll gradient. p53 protein levels were measured by fluorescence-activated cell sorting analysis and immunohistochemistry, using antibodies that recognize either the COOH terminus of RSp53 or ASp53. The results show that although less mature keratinocyte cells predominantly express the RSp53 form, the more mature cells preferentially express the ASp53 form. Therefore, it is possible that the two p53 forms are associated with different functions required at the various stages of keratinocyte differentiation. The results suggest that the COOH-terminal domain of the p53 molecule is important for its activity in the process of keratinocyte differentiation.

Alternative Splicing↗
PubMed1997

MIP-1alpha and MCP-1 differentially regulate acute and relapsing autoimmune encephalomyelitis as well as Th1/Th2 lymphocyte differentiation.

Chemokines are a family of small-molecular-weight cytokines that induce chemotaxis and chemokinesis of leukocytes. These molecules are ligands for seven-transmembrane, G-protein-linked receptors and are known to activate integrins on the surface of leukocytes and other cells as well as induce a number of signaling events. They play a significant role in the migration of leukocytes from blood into tissue during inflammatory processes. We tested the role of chemokines in experimental autoimmune encephalomyelitis (EAE) and found that macrophage inflammatory protein-1alpha (MIP-1alpha) correlated with acute disease development, whereas monocyte chemotactic protein-1 (MCP-1) did not. In contrast, MCP-1 production in the central nervous system correlated with relapsing EAE development. Moreover, anti-MIP-1alpha, but not anti-MCP-1, inhibited development of acute but not relapsing EAE, whereas anti-MCP-1 significantly reduced the severity of relapsing EAE. To test the effects of chemokines on the differentiation of naive T cells, TCR transgenic splenic T cells (Tg+ T cells) from DO11.10 OVA TCR transgenic mice were used as a source of Th0 cells and were stimulated with specific anti-clonotypic monoclonal antibodies in the presence of MIP-1alpha, MCP-1, or controls. MIP-1alpha drove Th0 cells to differentiate to Th1, whereas MCP-1 drove Th0 cells to differentiate to Th2. Similarly, MCP-1, but not MIP-1alpha significantly inhibited the adoptive transfer of EAE when included in in vitro activation cultures, further suggesting a regulatory anti-inflammatory property. These results suggest a differential role for CC chemokines in the development and activation of T cells during autoimmune inflammatory diseases.

Acute Disease↗
PubMed1998

Differential expression of Id genes in multipotent myeloid progenitor cells: Id-1 is induced by early-and late-acting cytokines while Id-2 is selectively induced by cytokines that drive terminal granulocytic differentiation.

Hematopoietic development is regulated by a complex mixture of cytokine growth factors that guide growth and differentiation of progenitor cell populations at different stages in their development. The genetic programs that drive this process are controlled at the molecular level by the type and number of transcriptional regulators coexpressed in the cell. Both positive- and negative-acting helix-loop-helix transcription factors are expressed during hematopoietic development, with the Id-type transdominant negative regulators controlling the net helix-loop-helix activation potential in the cell at any given time. It has been demonstrated that some of these Id factors are involved in the checkpoint at which undifferentiated progenitor cells make the commitment to terminal maturation. Therefore, we sought to determine whether these Id family factors are selectively induced or extinguished by cytokines that act at different points during hematopoiesis. NFS-60, a myeloid progenitor line that proliferates in response to multiple cytokines, was stimulated by treatment with SCF, IL-3, IL-6, G-CSF, and erythropoietin. Id-1 expression correlated tightly with cellular proliferation: it declined when growth factor stimulation was withdrawn and was quickly induced whenever the cell began to proliferate. The regulation of Id-2 was more complex: its expression was slightly upregulated in factor-deprived cells but only strongly reinduced after extended exposure to cytokines that drive granulocytic differentiation (IL-6, G-CSF, and TGFbeta). These data support a cell-cycle regulatory role for Id-1 in multipotent myeloid progenitor cells and a role for Id-2 during terminal granulocytic differentiation.

Cell Differentiation↗
PubMed1985

Differential requirements for the production by a T helper clone of the lymphokines involved in the induction of polyclonal proliferation and differentiation of unstimulated B lymphocytes.

Antigen-activated T helper (TH) cells secrete into their supernatant various lymphokines that are able to drive B cells to proliferate and to differentiate into Ig-secreting cells. In this report, we compared the production of these two types of activities by a TH clone. We found that B cell proliferating activity was released by TH cells under conditions in which T cell proliferation and the release of the B cell differentiating activity were totally blocked by anti-L3T4 monoclonal antibody GK1.5. The release of these two activities also dissociated during the reversion of T cells to the resting state after activation with antigen. Two weeks after activation, the T cell clone still secreted B cell proliferating activity, but did not secrete B cell differentiating activity. Three to four weeks after activation, neither activity was produced. The data suggest that the genes coding for these two activities are independently regulated in activated T cells. The implications of these observations concerning B lymphocyte development are discussed.

Animals↗
PubMed1993

Differential expression of leukocyte differentiation antigens in small round blue cell sarcomas.

BACKGROUND: Small round blue cell sarcomas (SRBCS) comprise a group of cytomorphologically poorly differentiated neoplasms that are characterized by different histogenesis and biologic behavior. METHODS: Twenty-seven well-characterized SRBCS were examined immunohistochemically to detect the expression of a panel of leukocyte differentiation (CD) antigens and class I (HLA-A,B,C) and class II (HLA-DR) major histocompatibility complex antigen. RESULTS: Although various cell surface antigens were detectable in SRBCS, the pan-leukocytic-histiocytic CD53 antigen was absent in the neoplastic population of all tumors studied; this finding allowed the authors to discriminate these lesions from lymphomas and leukemias. Some antigens had a differential pattern of expression in the SRBCS group, in particular in the undifferentiated tumor cell populations. In most instances, neuroblastomas (NB) and ganglioneuroblastomas (GNB) were CD9+/CD24+/CD56+ but CD40-/HLA-A,B,C-. Rhabdomyosarcomas (RMS) were CD56+ in all specimens and CD9+ in many samples; generally, they showed CD24-/CD40-/HLA-A,B,C-. Ewing sarcomas (ES) and peripheral primitive neuroectodermal tumors (pPNET) were HLA-A,B,C+/CD40+ but CD9-/CD24-/CD56- in most instances. Thus, with few exceptions, the expression of CD9 and CD56 and the simultaneous absence of HLA-A,B,C and CD40 differentiated GNB, NB, and RMS from ES and pPNET. GNB, NB, and RMS differed in regard to their CD24 expression. CONCLUSIONS: These data show that various types of SRBCS have different patterns of cell surface antigens. Therefore, these antigens are considered to be helpful in the immunophenotypic subclassification of SRBCS: The immunophenotypic similarities between ES and pPNET, however, might be an additional argument for a close relationship between these two lesions.

Antigens, CD↗
PubMed1985

Differential effects of the tumor promoter phorbol-12-myristate-13-acetate on the morphological and biochemical differentiation of N-18 mouse neuroblastoma cells.

The phorbol ester tumor promoter phorbol-12-myristate-13-acetate (PMA) was found to have differential inhibitory effects on the expression of morphological and biochemical differentiation of N-18 mouse neuroblastoma cells. PMA completely inhibited neurite extension and associated growth characteristics and partially inhibited the increased expression of R1 cAMP-binding protein; PMA had no effect on the induction of acetylcholinesterase activity in cells prompted to differentiate either by treatment with 1 mM dibutyryl cAMP or by serum deprivation. 4-alpha-Phorbol-12, 13-didecanoate, an inactive analogue of phorbol ester tumor promoter, was without effect. The implications of these findings concerning the mechanism of action of phorbol ester tumor promoters in the control of cell differentiation are discussed.

Acetylcholinesterase↗
PubMed2007

Cyclin I and p53 are differentially expressed during the terminal differentiation of the postnatal mouse heart.

In this study, we have used Ki-67 and MF20 mAb to determine how extensively cardiomyocytes proliferate in the postnatal mouse heart. It was established that the cardiomyocytes divided rapidly in 2-day-old hearts. However, at 13 days, the majority of cardiomyocytes had entered into terminal growth arrest and differentiation. We exploited this finding in order to identify proteins that were associated with cardiomyocyte growth and differentiation. The protein profiles of 2- and 13-day-old hearts were established by two-dimensional electrophoresis and compared. Seventeen protein spots were found to be differentially expressed at day 13. Eight of them were up-regulated while the remaining nine protein spots were down-regulated. We focused our attention on 2 of the proteins identified by MALDI-TOF MS, cyclin I and p53, because they are both believed to be involved in cell cycle regulation. Western blot analysis confirmed that both proteins were positively up-regulated in the 13-day-old postnatal heart. To determine directly whether these proteins were associated with cell proliferation, we examined their expression patterns in H9c2 cardiomyocytes maintained in vitro. We established that cyclin I expression was low during the growing phase of H9c2 culture and high during the growth arrest/differentiation phases. In contrast, p53 expression was unchanged during both phases. The various growth phases were confirmed by the presence of cyclin A and growth arrest-specific 1 proteins. We investigated whether silencing cyclin I expression using cyclin I-siRNA could promote an increase in H9c2 cell proliferation. It was determined that silencing cyclin I could enhance a small, but significant, increase in H9c2 cell division. Similar results were obtained for cardiomyocytes extracted from 13-day-old hearts. These results imply that the reason why cardiomyocytes in 13-day-old hearts increased cyclin I expression was probably associated with terminal growth arrest. However, the increase in p53 expression was probably associated with cardiomyocyte differentiation, rather than growth arrest.

Animals↗
PubMed1995

Isolation of cDNAs that are differentially expressed between androgen-dependent and androgen-independent prostate carcinoma cells using differential display PCR.

In the development of prostate cancer there is an important transition from androgen-dependent growth (which can be treated) to androgen-independent growth (which is beyond medical control). This transition is probably accompanied by genetic changes, resulting in the activation of oncogenes or the inactivation of tumor suppressor genes. In the present manuscript, the isolation of genes that may be involved in advanced, androgen-independent prostate cancer growth is described. Using differential display PCR, 13 cDNAs were isolated representing genes that are differentially expressed between the androgen-dependent prostate carcinoma cell line LN-CaP and the androgen-independent prostate carcinoma cell lines PC-3 and DU 145. These clones were divided into four groups: androgen-responsive genes (TL5, TL25, TL32, and TL35); genes with a marked decreased expression in one of the prostate cancer cell lines (TL27); genes with a marked, increased expression in one or more of the prostate cancer cell lines (TL4, TL16, TL21, and TL22); and genes with minor (but repeatable) changes in expression between prostate cancer cell lines (TL7, TL15, TL18, and TL33). The 13 genes were analyzed for their sequence information, tissue specificity, and androgen responsiveness in order to identify genes of interest. In summary, differential display PCR appears to provide an attractive alternative to existing molecular techniques to screen for differentially expressed genes in prostate cancer cells.

Androgens↗
PubMed1996

Combining the technique of RNA fingerprinting and differential display to obtain differentially expressed mRNA.

We have modified recently developed methods of RNA fingerprinting and differential display based on arbitrarily primed PCR which can be used for detection and cloning of differentially expressed mRNAs. Our protocol requires only a single cDNA synthesis for each different RNA sample, in contrast to the multiple cDNA reactions required for differential display method, followed by selective amplification of cDNA sequence fraction by arbitrary and oligo(dT) primers. We have shown that the longer primers (25-29-mers) allow the use of optimal dNTP concentration and higher stringency PCR. Further improvements include using TaqStart antibody for hot start PCR and thermostable enzyme mixes suitable for long-distance PCR. Long-distance PCR enables the method to display bands of up to 2 kb and should result in a higher fidelity of PCR products to the original RNA template. When these improvements are combined the resulting method is highly reproducible, and more than 85% of the differentially expressed bands can be confirmed by Northern blot analysis.

Adult↗
PubMed1985

On the mechanism of differential Giemsa staining of bromodeoxyuridine-substituted chromosomes. II. Differences between the demonstration of sister chromatid differentiation and replication patterns.

Experiments were performed to find out whether different mechanisms are involved in FPG-(fluorescent plus Giemsa) staining for the demonstration of replication patterns and sister chromatid differentiation (SCD) after bromodeoxyuridine (BrdU)-substitution of V79 Chinese hamster chromosomes. The influence of variations of the staining procedure on the quality of both SCD and replication patterns was comparatively investigated and differences in the demonstration of these two phenomena within the same chromosome were studied using various BrdU-labeling protocols. The results show that at least graduated differences exist. For a good differentiation of replication patterns a stronger FPG-treatment is necessary than it is for SCD. Partial BrdU substitution only leads to replication patterns in the next mitosis. A further round of replication either in the presence or absence of BrdU causes a reduced staining of the complete chromatid and three-way differentiation is seen in third generation mitoses. These results support the view that alterations of chromosomal proteins during BrdU-incorporation and replication of BrdU-substituted DNA are decisive for differential staining.

Animals↗
PubMed1991

Molecular approaches for analyzing differential gene expression: differential cDNA library construction and screening.

Complementary deoxyribonucleic acid (cDNA) libraries can be used as a means to isolate and identify cell-specific messenger ribonucleic acid (mRNA) sequences. The basic elements of cDNA library construction and screening are reviewed in the context of analyzing differentially expressed mRNAs. A brief overview of the recombinant DNA systems applied to cDNA library construction and the principles of screening cDNA libraries by plaque hybridization are provided. Methods for comparing mRNA populations by differential screening and by competition hybridization are discussed, and methods for constructing subtracted cDNA libraries, enriched in differentially expressed sequences, are presented. Also reviewed are the analysis of differentially expressed cDNAs by Southern and Northern hybridization, RNase protection, polymerase chain reaction, and sequencing.

Animals↗
PubMed2003

Pulmonary well-differentiated fetal adenocarcinoma expressing lineage-specific transcription factors (TTF-1 and GATA-6) to respiratory epithelial differentiation: an immunohistochemical and ultrastructural study.

A case of pulmonary well-differentiated fetal adenocarcinoma was examined with conventional histological, immunohistochemical, and ultrastructural studies that revealed the distribution of lineage-specific transcription factors (TTF-1 and GATA-6). The patient was a 33-year-old Japanese woman, who underwent resection of the right lower lobe for the lung tumor. The tumor demonstrated an organized histology mimicking the epithelial differentiation of fetal lung with peculiar glands and moruloid cell nests, without mesenchymal proliferation. Adenocarcinoma cells forming the atypical glands were similar to the epithelial cells of the branching tubules in the pseudo glandular stage of the fetal lung. Distribution of TTF-1 was observed in many of the nuclei of the adenocarcinoma cells forming the glands. Tumor cells in the morula were primitive epithelial cells with some immunohistochemical neuroendocrine cell differentiation and some of them showed GATA-6-positive stains in the nuclei. In the ultrastructural study, adenocarcinoma cells showed little differentiation toward mucous cells and ciliated cells. Neuroendocrine granules were seen in a few tumor cells in the morula. In the present case, tumor cells forming the peculiar histological, molecular, and ultrastructural constructions showed partial and incomplete mimicry of the morphogenesis of respiratory epithelium.

Adenocarcinoma↗
PubMed1992

Differential regulation of the transforming growth factor type-beta 2 gene promoter in embryonal carcinoma cells and their differentiated cells.

Previous studies have shown that EC cells do not express detectable levels of TGF-beta 2 or its mRNA until they differentiate. This suggested that differentiation influences the transcription of the TGF-beta 2 gene in this model system. To address this possibility, we have examined the activity of the TGF-beta 2 promoter in EC cells and their differentiated cells using gene constructs containing various portions of the TGF-beta 2 promoter inserted upstream of the reporter gene, chloramphenicol acetyltransferase (CAT). We determined that the level of CAT increases approximately ninefold when EC cells were induced to differentiate. Our studies also indicate that the TGF-beta 2 promoter contains at least two positive regulatory elements that are separated by a negative regulatory element. Finally, we have identified a CRE/ATF-like site that appears to be responsible for a positive regulatory element located between -77 and -40.

Base Sequence↗
PubMed1994

Surface contraction and expansion waves correlated with differentiation in axolotl embryos--I. Prolegomenon and differentiation during invagination through the blastopore, as shown by the fate map.

We have discovered a series of expansion and contraction, solitary waves that correlate with discrete steps of differentiation in the urodele amphibian axolotl embryo (Ambystoma mexicanum). Here we examine in detail the proposition that the blastopore is a set of differentiation waves. We superimposed the image of the axolotl fate map onto our digitized video images of normal gastrulation and matched the fate map to pigmentation irregularities on the embryo. We were then able to track the invagination of the fate map by tracking the variegated pigmentation on several embryos as gastrulation proceeded. We show a particular expansion and contraction wave sequence for every tissue in the blastula stage fate map and can now explain precisely why the fate map has the shape it does and its relationship to the embryo at subsequent stages. Each tissue can be assigned a differentiation code and placed on a hierarchical, binary differentiation tree.

Ambystoma mexicanum↗
PubMed1989

Differential responsiveness to phorbol esters correlates with differential expression of protein kinase C in KG-1 and KG-1a human myeloid leukemia cells.

The KG-1 myeloid leukemia cell line differentiates into macrophages in response to 12-O-tetradecanoylphorbol 13-acetate (TPA), while its spontaneous variant, the KG-1a cell line, is resistant to the differentiative effects of TPA. To determine the mechanism underlying these differential responses to TPA, experiments were performed to determine the relative numbers of TPA binding sites, protein kinase C (PKC) enzyme activity levels, PKC translocation responses and PKC gene expression in these cell lines. KG-1a cells exhibited 40% fewer high affinity binding sites for TPA than KG-1 cells. Although PKC translocation from cytosol to the membrane fraction was observed in both cell types, total PKC activity, measured in vitro using type III-S histone as substrate, was reduced by 70% in KG-1a cells. These biochemical differences between the parental line and the phorbol ester non-responsive variant were correlated with the depressed level of PKC-beta RNA abundance in KG-1a cells. Both lines expressed PKC-alpha RNA at comparable levels. Chronic exposure to TPA resulted in down-regulation of PKC enzyme activity in both cell lines, and a selective decrease in PKC-beta RNA transcripts in both cell types. In contrast, chronic TPA treatment had no effect on the levels of PKC-alpha RNA in KG-1 and KG-1a cells. Our results indicate a correlation between the level of PKC-beta expression and the responsiveness of myeloid lineage precursor cells to the differentiative effects of TPA.

Caenorhabditis elegans Proteins↗
PubMed2006

Differential receptor subunit affinities of type I interferons govern differential signal activation.

Type I interferons (IFNs) elicit antiviral, antiproliferative and immunmodulatory responses by binding to a shared cell surface receptor comprising the transmembrane proteins ifnar1 and ifnar2. Activation of differential response patterns by IFNs has been observed, suggesting that members of the family play different roles in innate immunity. The molecular basis for differential signaling has not been identified yet. Here, we have investigated the recognition of various IFNs including several human IFNalpha species, human IFNomega and human IFNbeta as well as ovine IFNtau2 by the receptor subunits in detail. Binding to the extracellular domains of ifnar1 (ifnar1-EC) and ifnar2 (ifnar2-EC) was monitored in real time by reflectance interference and total internal reflection fluorescence spectroscopy. For all IFNs investigated, competitive 1:1 interaction not only with ifnar2-EC but also with ifnar1-EC was shown. Furthermore, ternary complex formation was studied with ifnar1-EC and ifnar2-EC tethered onto solid-supported membranes. These analyses confirmed that the signaling complexes recruited by IFNs have very similar architectures. However, differences in rate and affinity constants over several orders of magnitude were observed for both the interactions with ifnar1-EC and ifnar2-EC. These data were correlated with the potencies of ISGF3 activation, antiviral and anti-proliferative activity on 2fTGH cells. The ISGF3 formation and antiviral activity correlated very well with the binding affinity towards ifnar2. In contrast, the affinity towards ifnar1 played a key role for antiproliferative activity. A striking correlation was observed for relative binding affinities towards ifnar1 and ifnar2 with the differential antiproliferative potency. This correlation was confirmed by systematically engineering IFNalpha2 mutants with very high differential antiproliferative potency.

Humans↗
PubMed1998

Identification of differentially expressed genes in human trophoblast cells by differential-display RT-PCR.

Molecular mechanisms controlling human trophoblast invasiveness are still poorly understood. In the present investigation, mRNA patterns of trophoblast cells isolated from first trimester (high invasiveness) and term placentae (no/low invasiveness) were compared by differential-display reverse transcriptase polymerase chain reaction (DDRT-PCR) revealing differential expression of numerous genes. Of 18 differentially expressed DDRT-PCR products analysed, 11 were unknown, four showed homologies with expressed sequence tag sequences, and three others were homologous to integrin-beta1, ATP-synthetase U6 (both showing higher expression in first trimester) or to aldose-reductase (higher expression at term), respectively. One of the unknown transcripts (PBK1, accession number: AJ007398) was cloned from a first trimester placenta cDNA library and was characterized. The 1908-bp gene fragment contains an open reading frame of 1551 bp and an Alu-sequence in the 3' non-coding region. According to Northern blot analysis on JAr choriocarcinoma cells, the fragment is close to full-length cDNA. By in situ hybridization, PBK1 was detected only in first trimester but not term placentae in the proximal parts of cell islands and in closely adjacent villous cytotrophoblast. This expression pattern suggests that the newly identified molecule, PBK1, could be involved in the regulation of proliferation/ differentiation and potentially in invasion of trophoblast cells.

ATP Synthetase Complexes↗