Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “CELL DIFFERENTIATION”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 451 records · Page 25Linked to original sources
PubMedDate not supplied

The distribution of connexin 43 is associated with the germ cell differentiation and with the modulation of the Sertoli cell junctional barrier in continual (guinea pig) and seasonal breeders' (mink) testes.

To test whether the gap junction protein connexin 43 (Cx43) is associated with germ cell differentiation and with the Sertoli cell junctional blood barrier, we recorded the temporal changes in its distribution before birth, through the neonatal period, puberty, and adulthood in guinea pig, and throughout the annual seasonal reproductive cycle in the mink. We used the immunoperoxidase labeling technique on Bouin's perfused-fixed testes and with site-specific polyclonal affinity-purified antibodies against Cx43. Cx43 was localized between Leydig cells in fetal guinea pig testis. In this species, after birth, the appearance of Cx43 concurred with the onset of spermatogenesis. In the seminiferous epithelium, the distribution of Cx43 coincided with the gap junctions of the Sertoli cell junctional blood barrier. In guinea pig and mink, the distribution of the protein in the tubules changed in accordance with the germ cell differentiation in a stage-dependent manner and with the modulation, i.e., the assembly and disassembly of the junctional barrier accompanying the translocation of spermatocytes into the lumenal compartment. In the mink, the reaction product persisted during testicular regression but showed a similar distribution from one tubule to the next. In this paper, we documented the existence of a temporal correlation between the appearance of the gap junction protein Cx43 and both the germ cell differentiation and the modulation in the junctional barrier between Sertoli cells. The paper also discusses the possibility that cell-to-cell communications, generally attributed to gap junctions, may help changes in the barrier to take place in coordination with spermatogenesis.

Animals↗
PubMed2002

Cord blood CD34+ cells differentiate into dermal dendritic cells in co-culture with cutaneous fibroblasts or stromal cells.

The skin is a unique organ that contains two different subsets of dendritic cells, i.e., Langerhans cells and dermal dendritic cells. Our hypothesis is that cutaneous fibroblasts may affect the development of these dendritic cells. We cocultured cord blood CD34+ hematopoietic progenitor cells with several human cutaneous fibroblast cell lines without any exogenous cytokines for 3 wk. In this culture, hematopoietic progenitor cells increased in number from 20.1 +/- 2.4 times, and produced aggregates of cells with dendritic processes. They were composed of 54.9 +/- 3.2% HLA-DR+ CD14+ CD1a-- cells and 13.8 +/- 3.6% HLA-DR+ CD1a+ cells, which also expressed CD11b and CD11c. There were significant numbers of factor XIIIa+ cells in the culture, whereas no Lag+ or E-cadherin+ cells were detected, and they were potent stimulators in allogeneic T cell activation. There was a significant difference in the ability to induce CD1a+ cells among different human cutaneous fibroblast cell lines. These CD1a+ cells lacked the expression of CD80, CD86, or CD83. In addition, half of them still expressed CD14. When these dendritic cells were cultured with tumor necrosis factor-alpha, however, they became mature dendritic cells with augmented expression of CD86 and CD83 and with increased allogeneic T cell stimulation. The subsequent experiment using a dividing chamber, enzyme-linked immunosorbent assay for granulocyte-macrophage colony-stimulating factor and macrophage colony-stimulating factor, and the blocking studies with antibodies for these cytokines suggested that both the presence of direct contact between hematopoietic progenitor cells and human cutaneous fibroblast cell lines and macrophage colony-stimulating factor produced by human cutaneous fibroblast cell lines are required for their maximum growth and differentiation into CD1a+ dendritic cells, whereas macrophage colony-stimulating factor was solely responsible for their differentiation. These data suggest that cutaneous fibroblasts support the differentiation of dermal dendritic cells in addition to that of monocytes from hematopoietic progenitor cells by their direct contact with hematopoietic progenitor cells and by their macrophage colony-stimulating factor production.

Antigen-Presenting Cells↗
PubMed2002

[The relationship of p53 gene mutation to cell differentiation and metastasis of laryngeal squamous cell carcinoma].

OBJECTIVE: To inquire about the relationship of p53 gene mutation to the histopathological findings and clinical manifestation in cases of laryngeal squamous cell carcinoma(LSCC). METHODS: The fresh samples from 60 cases of LSCC were examined. Polymerase chain reaction and silver staining-single strand conformation polymorphism (PCR-SSCP) and DNA direct sequencing were used to detect the mutation of p53 gene in exons 5-8. RESULTS: The mutation rates were 69.2% and 85.3% in patients at clinical stage I-II and stage III-IV respectively (P>0.05). In the well-, moderately- and poorly-differentiated cell of LSCC, the mutation rates were 52.9%, 83.3% and 94.7% respectively (P<0.05). The p53 gene mutation rate of LSCC patients with neck lymph-node metastasis was 96.4%, whereas that of patients without neck lymph-node metastasis was 62.5% (P<0.05). Twenty samples showed positive results in SSCP; 19 samples showed deletion and mutation in codons 125-292 by DNA direct sequencing. CONCLUSION: The mutation of p53 gene in exons 5-8 was closely related to cell differentiation and the neck lymph-node metastasis of LSCC, but it was not related to the clinical stages of the LSCC cases.

Carcinoma, Squamous Cell↗
PubMed1989

Intracellular Ca2+ potentiates Na+/H+ exchange and cell differentiation induced by phorbol ester in U937 cells.

The human cell line U937 differentiates to monocyte macrophage-like cells in response to tumour-promoting phorbol esters. This effect is attributed to activation of protein kinase C. We show here that U937 cell differentiation induced by 12-O-tetradecanoylphorbol 13-acetate (TPA) is associated with cytoplasmic alkalinization. Ethyl-isopropyl-amiloride (EIPA), a potent inhibitor of Na+/H+ exchange, blocked both cytoplasmic alkalinization and cell differentiation. Cell acidification by addition of 2-4 mM sodium propionate also blocked TPA-induced U937 cell differentiation. These results suggest that a sustained cell alkalinization mediated by activation of Na+/H+ exchange is essential for TPA-induced differentiation in U937 cells. The increase of cytoplasmic free calcium concentration ([Ca2+]i) by addition of the calcium ionophore ionomycin enhanced TPA-induced alkalinization by increasing the apparent affinity of the Na+/H+ antiporter for intracellular H+. Treatment with ionomycin also potentiated differentiation of U937 cells induced by TPA. This synergism suggests that [Ca2+]i either potentiates the activation of protein kinase C or triggers additional transducing mechanisms. The key events of this interaction occur during the first 30 min of treatment, even though cell differentiation manifests much later.

Amiloride↗
PubMed2006

Characteristics of rat bone marrow cells differentiated into a liver cell lineage and dynamics of the transplanted cells in the injured liver.

BACKGROUND: Bone marrow cells (BMCs) have been shown to differentiate into a liver cell lineage, but little is known about their dynamics following transplantation. BMCs were cultured to investigate the expression of liver-specific genes in vitro and transplanted into in vivo liver-injury models to elucidate their dynamics in the liver. METHODS: The mRNA expression of various liver-specific genes in BMCs cocultured with hepatocytes was analyzed using reverse transcription-polymerase chain reaction. BMCs from transgenic rats expressing green fiuorescent protein were transplanted into the spleen of rat liver-injury models induced with 2-acetylaminofiuorene (2-AAF) or carbon tetrachloride (CCl4). BMCs were also transplanted directly into livers treated with CCl4 to determine which route is better for transplantation. RESULTS: BMCs differentiated into a liver cell lineage in vitro and expressed mRNAs consistent with mature hepatocytes, including albumin. The transplanted BMCs were found in the liver in the CCl4-induced injury model, but not in the 2-AAF-induced model. The hepatocyte growth factor and fibroblast growth factor mRNA levels in the liver were significantly higher in the CCl4-induced model than in the 2-AAF-induced model. Migration of BMCs to the liver was more effective following injection into the liver, rather than into the spleen. CONCLUSIONS: Cultured BMCs differentiated into a liver cell lineage are a potential source for cell transplantation. Transplantation is successful in the severely injured liver with a high level of expression of mRNAs for growth factors. Injection of BMCs directly into the liver is the preferred route of administration.

2-Acetylaminofluorene↗
PubMed2003

Effect of IGF-1 and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the expression of LH receptors during cell differentiation in cultured granulosa cells.

Ovarian granulosa cells undergo a complex differentiation process during the growth and maturation of ovarian follicle. This process includes the acquisition of cell surface LH receptor, which mediates the granulosa cell's ability to respond to circulating LH. The results of the actions of LH on the mature granulosa cell include steroidogenesis, luteinization, and ovulation. As such, induction of the LH receptor in granulosa cells is a critical step in reproductive physiology. In the present study, we attempted to assess the effects of IGF-1 and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on FSH-induced LH receptor expression in rat granulosa cells to understand the actions of these factors on normal reproductive function. Treatment with FSH, as expected, produced a substantial increase in LH receptor mRNA level, and concurrent treatment with increasing concentrations of IGF-1 brought about dose-dependent increases in FSH-induced LH receptor mRNA. On the other hand, the concurrent treatment of TCDD (10 pM) resulted in a significant decrease in LH receptor after 24 h. The decay curves for LH receptor mRNA transcript showed a significant increase in the half-life after the addition of IGF-1 and a significant decrease after addition of TCDD. These data suggests a possible role for changes in LH receptor mRNA stability in the IGF-1 and TCDD induced regulation of LH receptor in rat granulosa cells. The rates of LH receptor mRNA gene transcription, assessed by nuclear run-on transcription assay, were not increased by the addition of IGF-1, but decreased by the addition of TCDD. The data of IGF-1 present that the interface between circulating hormones and paracrine/autocrine systems could provide an important mechanism to amplify the effects of gonadotropin hormones at the local level. In addition, the endocrine-disrupting effects of TCDD are, at least in part, caused by direct action on the expression of LH receptor expression in granulosa cells.

Animals↗
PubMed2003

Gene expression profiling during all-trans retinoic acid-induced cell differentiation of acute promyelocytic leukemia cells.

Using cDNA microarrays we determined the gene expression patterns in the human acute promyelocytic leukemia (APL) cell line NB4 during all-trans retinoic acid (ATRA)-induced differentiation. We analyzed the expression of 12,288 genes in the NB4 cells after 12 hours, 24 hours, 48 hours, 72 hours, and 96 hours of ATRA exposure. During this time course, we found 168 up-regulated and more than 179 down-regulated genes, most of which have not been reported before. Many of the altered genes encode products that participate in signaling pathways, cell differentiation, programmed cell death, transcription regulation, and production of cytokines and chemokines. Of interest, the CD52 and protein kinase A regulatory subunit alpha (PKA-Rlalpha) genes, whose products are being used as therapeutic targets for certain human neoplasias in currently ongoing clinical trials, were among the genes observed to be markedly up-regulated after ATRA treatment. The present study provides valuable data to further understand the mechanism of ATRA-induced APL cell differentiation and suggests potential therapeutic alternatives for this leukemia.

Apoptosis↗
PubMed2003

Transplanted adult hematopoietic stems cells differentiate into functional endothelial cells.

During early embryogenesis, blood vessels and hematopoietic cells arise from a common precursor cell, the hemangioblast. Recent studies have identified endothelial progenitor cells in the peripheral blood, and there is accumulating evidence that a subset of these cells is derived from precursors in the bone marrow. Here we show that adult bone marrow-derived, phenotypically defined hematopoietic stem cells (c-kit+, Sca-1+, lineage-) give rise to functional endothelial cells. With the exception of the brain, donor-derived cells are rapidly integrated into blood vessels. Durably engrafted endothelial cells express CD31, produce von Willebrand factor, and take up low-density lipoprotein. Analysis of DNA content indicates that donor-derived endothelial cells are not the products of cell fusion. Self-renewal of stem cells with hematopoietic and endothelial cell potential was revealed by serial transplantation studies. The clonal origin of both hematopoietic and endothelial cell outcomes was established by the transfer of a single cell. These results suggest that adult bone marrow-derived hematopoietic stem cells may serve as a reservoir for endothelial cell progenitors.

Animals↗
PubMed1999

Polyglutamylation and polyglycylation of alpha- and beta-tubulins during in vitro ciliated cell differentiation of human respiratory epithelial cells.

Tubulins are the major proteins within centriolar and axonemal structures. In all cell types studied so far, numerous alpha- and beta-tubulin isoforms are generated both by expression of a multigenic family and various post-translational modifications. We have developed a primary culture of human nasal epithelial cells where the ciliated cell differentiation process has been observed and quantified. We have used this system to study several properties concerning polyglutamylation and polyglycylation of tubulin. GT335, a monoclonal antibody directed against glutamylated tubulins, stained the centriole/basal bodies and the axonemes of ciliated cells, and the centrioles of non-ciliated cells. By contrast, axonemal but not centriolar tubulins were polyglycylated. Several polyglutamylated and polyglycylated tubulin isotypes were detected by two-dimensional electrophoresis, using GT335 and a specific monoclonal antibody (TAP952) directed against short polyglycyl chains. Immunoelectron microscopy experiments revealed that polyglycylation only affected axonemal tubulin. Using the same technical approach, polyglutamylation was shown to be an early event in the centriole assembly process, as gold particles were detected in fibrogranular material corresponding to the first cytoplasmic structures involved in centriologenesis. In a functional assay, GT335 and TAP952 had a dose-dependent inhibitory effect on ciliary beat frequency. TAP952 had only a weak effect while GT335 treatment led to a total arrest of beating. These results strongly suggest that in human ciliated epithelial cells, tubulin polyglycylation has only a structural role in cilia axonemes, while polyglutamylation may have a function both in centriole assembly and in cilia activity.

Cell Differentiation↗
PubMed1985

Production of PDGF-like growth factors by embryonal carcinoma cells and binding of PDGF to their endoderm-like differentiated cells.

In this report, we demonstrate that F9 and PC-13 embryonal carcinoma (EC) cells do not bind significant amounts of platelet-derived growth factor (PDGF), whereas the endoderm-like differentiated cells derived from EC cells do. The F9-differentiated cells exhibit approximately 8300 receptors per cell, with an apparent dissociation constant of 30 pM. Two endoderm-like cell lines, PSA-5E and PYS-2, also bind PDGF and exhibit approximately 4800 and 23,500 receptors per cell, respectively. The lack of PDGF binding by the parental EC cells is consistent with their release of a factor(s) that is closely related to PDGF. This factor(s) competes with PDGF for binding to membrane receptors and is recognized by antibodies raised against PDGF. However, this factor(s) does not appear to be antigenically identical to PDGF. We also show that production of this PDGF-like factor(s) is reduced more than 90% when F9 EC cells differentiate into cells that bind PDGF. Thus, our findings indicate that EC cells release a factor(s) that should be capable of binding to their differentiated cells. This raises the possibility that PDGF, or a closely related factor, can influence cell proliferation and/or cell behavior of early embryonic cells.

Animals↗
PubMed2002

A role for p53 in terminal epithelial cell differentiation.

Terminal epithelial cell differentiation is a crucial step in development. In the kidney, failure of terminal differentiation causes dysplasia, cystogenesis, and cancer. The present study provides multiple lines of evidence implicating the tumor suppressor protein p53 in terminal differentiation of the renal epithelium. In the developing kidney, p53 is highly enriched in epithelial cells expressing renal function genes (RFGs), such as receptors for vasoactive hormones, the sodium pump, and epithelial sodium and water channels. In comparison, proliferating renal progenitors express little if any p53 or RFGs. p53 binds to and transactivates the promoters of RFGs. In contrast, expression of a dominant negative mutant form of p53 inhibits endogenous RFG expression. Moreover, binding of endogenous p53 to the promoters of RFGs coincides with the differentiation process and is attenuated once renal epithelial cells are fully differentiated. Finally, p53-null pups exhibit a previously unrecognized aberrant renal phenotype and spatial disorganization of RFGs. Interestingly, the p53-related protein p73 is unable to functionally compensate for the loss of p53 and fails to efficiently activate RFG transcription. We conclude that p53 promotes the biochemical and morphological differentiation of the renal epithelium. Aberrations in p53-mediated terminal differentiation may therefore play a role in the pathogenesis of nephron dysgenesis and dysfunction.

Animals↗
PubMed2003

Regulation of MyoD activity and muscle cell differentiation by MDM2, pRb, and Sp1.

Muscle cell differentiation is controlled by a complex set of interactions between tissue restricted transcription factors, ubiquitously expressed transcription factors, and cell cycle regulatory proteins. We previously found that amplification of MDM2 in rhabdomyosarcoma cells interferes with MyoD activity and consequently inhibits overt muscle cell differentiation (1). Recently, we found that MDM2 interacts with Sp1 and inhibits Sp1-dependent transcription and that pRb can restore Sp1 activity by displacing MDM2 from Sp1 (2). In this report, we show that forced expression of Sp1 can restore MyoD activity and restore overt muscle cell differentiation in cells with amplified MDM2. Furthermore, we show that pRb can also restore MyoD activity and muscle cell differentiation in cells with amplified MDM2. Surprisingly, we found that the MyoD-interacting domain of pRb is dispensable for this activity. We show that the C-terminal, MDM2-interacting domain of pRb is both necessary and sufficient to restore muscle cell differentiation in cells with amplified MDM2. We also show that the C-terminal MDM2-interacting domain of pRb can promote premature differentiation of proliferating myoblast cells. Our data support a model in which the pRb-MDM2 interaction modulates Sp1 activity during normal muscle cell differentiation.

3T3 Cells↗
PubMed2002

Identification of an S-adenosylhomocysteine hydrolase-like transcript induced during dendritic cell differentiation.

Dendritic cells (DC) are the professional antigen-presenting cells that initiate immune responses. While DC take up antigen, migrate to lymph nodes and present processed antigen to T lymphocytes, little is known of the intracellular biochemical pathways controlling these events. Using the differential display technique, employing the activated blood DC-like cell line L428, we isolated a cDNA induced during DC differentiation likely to have a regulatory function. This cDNA encoded a putative 530-amino-acid (aa) protein consisting of a unique hydrophilic domain (106 aa) and a domain (424 aa) similar to the methylation pathway enzyme S-adenosylhomocysteine hydrolase (AHCY). Therefore, this molecule was termed DC-expressed AHCY-like molecule (DCAL). DCAL mRNA was expressed moderately in fresh blood DC, but was not detectable in other peripheral blood mononuclear cells. DCAL mRNA increased markedly during activation of blood and skin DC (Langerhans cells), but was diminished in terminally differentiated tonsil DC. Cultured monocytes expressed little DCAL mRNA, but levels increased markedly when differentiated into DC by cytokines GM-CSF and IL-4. The DCAL gene [Chromosome (Chr) 1] and another previously identified DCAL-like molecule KIAA0828 (Chr 7) differed from the AHCY gene (Chr 20) in gene organization. Thus, DCAL may have a role in controlling critical events in DC differentiation and belong to a novel family of AHCY-like molecules.

Adenosylhomocysteinase↗
PubMed2006

ERK signaling is a molecular switch integrating opposing inputs from B cell receptor and T cell cytokines to control TLR4-driven plasma cell differentiation.

Differentiation of B cells into plasma cells represents a critical immunoregulatory checkpoint where neutralizing Abs against infectious agents must be selected whereas self-reactive Abs are suppressed. Bacterial LPS is a uniquely potent bacterial immunogen that can bypass self-tolerance within the T cell repertoire. We show here that during LPS-induced plasma cell differentiation, the ERK intracellular signaling pathway serves as a pivotal switch integrating opposing inputs from Ag via BCR and from the two best characterized B cell differentiation factors made by T cells, IL-2 and IL-5. Continuous Ag receptor signaling through the RAS/MEK/ERK pathway, as occurs in self-reactive B cells, inhibits LPS induction of Blimp-1 and the plasma cell differentiation program. Differentiation resumes after a transient pulse of Ag-ERK signaling, or upon inactivation of ERK by IL-2 and IL-5 through induction of dual-specificity phosphatase 5 (Dusp5). The architecture of this molecular switch provides a framework for understanding the specificity of antibacterial Ab responses and resistance to bacterially induced autoimmune diseases such as Guillain-Barré syndrome.

Animals↗
PubMed1993

HIV-gp 160-induced T cell-dependent B cell differentiation. Role of T cell-B cell activation molecule and IL-6.

The HIV envelope glycoprotein gp160 has been previously demonstrated to induce differentiation of normal B lymphocytes into Ig-secreting cells; the response is T cell-dependent, and T cells pretreated with gp160 can support B cell differentiation. This study investigates the cell surface molecules and cytokines that play a role in the gp160-induced T-B cell interaction. Utilizing CD4+CD45RO+ cloned T cells as the source of helper cells, we observed that physical contact with B cells is essential for the gp160-induced B cell response; no IgG-secretion occurred if T cells were separated from the B cells by culturing them in Transwell chambers. The expression of T cell-B cell activation molecule, a novel surface molecule associated with T cell activation, was moderately increased by gp160, and antibody to T cell-B cell activation molecule abrogated the gp160-mediated Th cell function. Cell surface molecules LFA-1, ICAM-1, HLA-DR, CD28, and B7 were also involved in the T-B cell interaction since mAb to any of these molecules inhibited the gp160-induced B cell differentiation response. gp160 also induced IL-6R and CD23 molecule expression on B cells when added to cultures of T plus B cells; there was CD23 expression only in cells that formed conjugates with T cells. Paraforamaldehyde-fixed, gp160-pretreated T cells failed to elicit IgG responses in B cells, but did induce CD23 and IL-6R up-regulation on B cells. Addition of exogenous IL-6, but not IL-2 or IL-4, restored the IgG secretion. These findings indicate that the T cell dependence for gp160-induced B cell differentiation responses involves two steps: one requires contact-dependent interaction of several cell surface molecules, and the second requires IL-6 secretion.

Antigens, Differentiation, B-Lymphocyte↗
PubMed1982

Surface markers of cloned human T cells with helper or suppressor activity on pokeweed mitogen-driven B cell differentiation.

Human spleen T cells stimulated with pokeweed mitogen (PWM) were cloned under limiting conditions in microculture systems using interleukin 2 and irradiated autologous cells. Clones were screened for helper or suppressor activity on PWM-dependent B cell differentiation by adding cell aliquots to either isolated B cells and PWM or to mixtures of T and B cells and PWM. Out of 97 clones tested, 14 promoted intense B cell differentiation, as assessed by measurements of secreted IgG, and 6 strongly inhibited B cell maturation induced by spleen T cells. All the selected clones maintained their original activity after short-term clonal expansion; in addition, a similar (helper or suppressor) effect was detected when the total number of plasma cells per well was evaluated. Suppressor clones had no cytolytic activity on autologous T and B cell blasts, K562 cells or antibody-coated L 1210 mouse cells. Nine helper and 6 suppressor clones were analyzed for a battery of surface markers. All the clones were E rosette-positive and expressed HLA-DR (Ia) antigens. Fcmu receptor was present on a single helper clone, whereas Fc gamma receptor was expressed on a suppressor clone only. All but two clones expressed the OKT4+/ OKT8-, a single suppressor clone was OKT8+/OKT4-, whereas coexpression of OKT4 and OKT8 antigens was detected in one helper clone. Thus, the claim that helper T cells are OKT4+/OKT8- and suppressor T cells are OKT4-/OKT8+ is not supported by the analysis of their phenotype at the clonal level.

Antibodies, Monoclonal↗
PubMed1988

Tumor promoters induce a transient expression of tumor-associated genes in both basal and differentiated cells of the mouse epidermis.

The effect of tumor promoters on the in vivo expression of tumor-associated, overexpressed genes was studied. Two of the tumor-associated genes, mal 1 and mal 2 were overexpressed already in the benign papilloma stage of mouse skin carcinogenesis. Overexpression of the other two genes, mal 4 and transin, was specific for the malignant state. Treatment of the normal adult epidermis with the complete tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) and the incomplete, second-stage promoter 12-O-retinylphorbol-13-acetate (RPA) enhanced transiently the expression of the mal sequences and transin. Fractionation of the adult epidermis on Percoll gradients into basal cells and differentiated, suprabasal cells showed that expression of the mal sequences was enhanced by TPA in both basal and differentiated cells. In contrast, transin expression, which was undetectable in cells of the normal epidermis, was enhanced in only the basal cells of the TPA-treated epidermis. The non-tumor-promoting hyperplastic agent, ethylphenyl propiolate (EPP), applied to the skin at a hyperplastic dose level did not enhance the expression of the mal 4 or transin sequences in the epidermis and had only a slight enhancing effect on the levels of mal 1 and mal 2 transcripts in the epidermis. Our results suggest that the observed stimulated expression of mal 1 and mal 2 is related to proliferative processes, whereas stimulated expression of mal 4 and transin reflects tumor-promoter-specific responses.

Animals↗
PubMed1991

Trophoblast cell differentiation: establishment, characterization, and modulation of a rat trophoblast cell line expressing members of the placental prolactin family.

The purpose of this investigation was to establish and characterize a cell line derived from a rat choriocarcinoma and to evaluate the usefulness of the cell line as an in vitro model for studying trophoblast cell differentiation. A cell line was generated from choriocarcinoma explants and named Rcho-1. The cell line consisted of a mixture of cell types, including small cells growing in clusters and giant cells possessing very large nuclei. This characteristic morphology was maintained through at least 23 passages and in a series of clonal cell lines isolated from the parent Rcho-1 cell line. The Rcho-1 cell line was capable of expressing placental lactogen-I (PL-I), PL-II, PRL-like protein-A (PLP-A), and PLP-C mRNAs when cultivated in vitro; however, the Rcho-1 cells expressed only PL-I when grown beneath the kidney capsule of host rats. The Rcho-1 cell line did not express PLP-B under any experimental condition. This pattern of placental PRL expression was maintained for 23 passages. Rcho-1 cells synthesized and secreted PL-I, PL-II, and PLP-A proteins with biochemical characteristics similar to those of their placental counterparts. PL-I and PL-II mRNAs were specifically localized to giant cells. Morphological appearance and placental PRL expression were used as indices for monitoring the differentiation state of Rcho-1 cells grown under various conditions. Both morphological and functional trophoblast cell differentiation were induced by maintaining the Rcho-1 cells in postconfluent culture conditions. Postconfluent Rcho-1 cultures were characterized by an increased percentage of giant cells and an induction of placental PRL expression. Some clonal cell lines derived from the parent Rcho-1 cell line exhibited distinct patterns of differentiation and placental PRL expression. In summary, we have established a rat trophoblast cell line capable of expressing a differentiated phenotype. The differentiated phenotype includes both morphological and functional parameters and can be modulated in vitro. This cell line is a unique model for studying the control of placental PRL gene expression and the regulation of trophoblast cell differentiation.

Animals↗