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At least 649 records · Page 36Linked to original sources
PubMed2006

Glomerular epithelial cells transform to myofibroblasts: early but not late removal of TGF-beta1 reverses transformation.

Studies were carried out to determine whether epithelial-mesenchymal transformation (EMT), well described in renal tubular epithelial cells, also occurs in glomerular epithelial cells and whether it is reversible. To this effect, cultured glomerular epithelial cells were incubated with TGF-beta(1) and their transformation into myofibroblasts was studied. At 4 days, the cells altered their phenotype, as shown by a change in shape, an increase in intracellular staining for alpha-smooth muscle actin (alpha-SMA), a decrease in membrane staining for cytokeratin, and an increase in matrix deposition. Changing the medium after 4 days by excluding TGF-beta(1) and adding fetal bovine serum (FBS) [as a source of epidermal growth factor (EGF) and other growth factors] caused the cells to revert to their original epithelial phenotype. By contrast, when the medium was changed in the same manner after 8 days of exposure to TGF-beta(1), the cells did not revert but remained myofibroblastic. Staining the cells for expression of EGF receptor before and after exposure to TGF-beta(1) caused this receptor, originally present on the plasma membrane, to become partly intracellular after 4 days of TGF-beta(1) exposure and completely intracellular after 8 days of TGF-beta(1) exposure. Kidney sections from 2 models of renal mass reduction were stained. Loss of the epithelial marker (podocalyxin) staining and the acquisition of alpha-SMA staining was observed in the glomeruli. It is concluded that EMT takes place in glomerular epithelial cells in vivo and in vitro. In cultured glomerular epithelial cells, the process can be reversed by early, but not late intervention. It seems that TGF-beta(1) exposure progressively downregulates the EGF receptor on the membrane, rendering the cell refractory to EGF signals critical for maintaining the epithelial phenotype.

Actins↗
PubMed2004

Fourier transform infrared (FTIR) spectral mapping of the cervical transformation zone, and dysplastic squamous epithelium.

OBJECTIVES: This paper is aimed at establishing infrared spectral patterns for the different tissue types found in, and for different stages of disease of squamous cervical epithelium. Methods for the unsupervised distinction of these tissue types are discussed. METHODS: Fourier transform infrared (FTIR) maps of the squamous and glandular cervical epithelium, and of the cervical transformation zone, were obtained and analyzed by multivariate unsupervised hierarchical cluster methods. The resulting clusters are correlated to the corresponding stained histopathological features in the tissue sections. RESULTS: Multivariate statistical analysis of FTIR spectra collected for tissue sections permit an unsupervised method of distinguishing tissue types, and of differentiating between normal and diseased tissue. By analyzing different spectral windows and comparing the results with histology, we found the amide I and II region (1740-1470 cm(-1)) to be very important in correlating anatomical and histopathological features in tissue to spectral clusters. Since an unsupervised, rather than a diagnostic, algorithm was used in these efforts, no statistical analysis of false-positive/false-negative results is reported at this time. CONCLUSIONS: The combination of FTIR micro-spectroscopy and multivariate spectral processing provides important insights into the fundamental spectral signatures of individual cells and consequently shows potential as a diagnostic tool for cervical cancer.

Cell Transformation, Neoplastic↗
PubMed1992

A novel compound, depudecin, induces production of transformation to the flat phenotype of NIH3T3 cells transformed by ras-oncogene.

A novel compound, depudecin, induced production of the flat phenotype of Ki-ras-transformed NIH3T3 cells at the low concentration of 1 microgram/ml. This effect was reversible. Actin stress fiber was detected in these cells after depudecin treatment. Almost complete reversion to the flat phenotype was observed at 6 h after depudecin addition. The synthesis of ras-mRNA did not decrease enough with depudecin treatment at the concentration of 10 micrograms/ml to reverse the transformed morphology.

3T3 Cells↗
PubMed1998

Malignant transformation of duct-like cells originating from acini in transforming growth factor transgenic mice.

BACKGROUND & AIMS: In transgenic mice overexpressing transforming growth factor (TGF)-alpha in the exocrine pancreas, progressive pancreatic fibrosis and a transdifferentiation of acinar cells to duct-like cells occurs. The present study was undertaken to analyze this transdifferentiation process. METHODS: Pancreatic specimens were characterized using light microscopy and immunohistochemistry. Expression of the epidermal growth factor receptor (EGFR) and TGF-alpha was evaluated with slot blot and Western analysis. To identify other generic events, K-ras mutations were screened with an enriched polymerase chain reaction approach and p53 expression was detected with immunohistochemistry. RESULTS: Morphological examination revealed an aggregation of interlobular fibroblasts and a decrease in acinar cell height starting at day 14 after birth. In older animals, these acinar cells change to duct-like cells, which form tubular structures and express ductal markers. Evidence for dysplastic changes was found in 12 of 21 TGF-alpha transgenic mice older than 1 year. We also observed four malignant pancreatic tumors, which were multicentric and originated from dysplastic tubular complexes. They displayed a mixed cystic-papillary phenotype strongly positive for carbonic anhydrase activity. EGFR expression progressively increased in the transition from acinar to duct-like and transformed cells. Activating K-ras mutations could not be detected; however, tubular complexes and tumors displayed increased immunoreactivity for nuclear p53. CONCLUSIONS: These data suggest an involvement of the TGF-alpha/EGFR pathway in conjunction with other yet unknown events in pancreatic tumor development. Furthermore, these observations are in favor of an acinar-ductal carcinoma sequence. Thus, these transgenic animals will be useful to define genetic alterations associated with a transition from acinar cells to a neoplastic ductal phenotype.

Animals↗
PubMed1998

Possible involvement of transforming growth factor-beta 1 and transforming growth factor-beta receptor type II during luteinization in the marmoset ovary.

The expression of transforming growth factor-beta 1 (TGF-beta 1), and transforming growth factor-beta receptor type II (T beta R-II), were evaluated in periovulatory marmoset ovaries. Histochemical methods were used, in particular double-labelling techniques, in order to correlate growth factor/receptor expression with proliferation (Ki 67), apoptosis (TUNEL method) and luteinization (3 beta-hydroxysteroid dehydrogenase (3 beta-HSD)). The latter was used as a luteinization marker. Periovulatory ovaries are especially suited for studying all aspects since they typically consist of small non-luteinized follicles, large luteinizing follicles and corpora lutea accessoria (Clas), which have developed from large luteinizing follicles. TGF-beta 1 and T beta R-II expression was found in luteinizing theca cells of large periovulatory follicles and in all luteal cells of Clas. Non-luteinized theca cells, including those of small follicles were always devoid of any immunostaining. Granulosa cells of small follicles were immunopositive for T beta R-II. Large follicles with granulosa cell immunoreactivity of both antibodies coexisted with non-reactive follicles of comparable size. The highest activity of the luteal marker enzyme 3 beta-HSD was co-localized in the same cells that expressed TGF-beta 1 and T beta R-II. The double-labelling experiments revealed that TGF-beta 1 and T beta R-II expression is not correlated with proliferation or apoptosis of follicular cells. Our results indicate that TGF-beta 1 and T beta R-II participate in differentiation processes, i.e. luteinization, rather than proliferation. In particular, the dynamics of T beta R-II expression appear highly related to the process of luteinization.

3-Hydroxysteroid Dehydrogenases↗
PubMed1983

Transforming growth factors produced by retrovirus-transformed rodent fibroblasts and human melanoma cells: amino acid sequence homology with epidermal growth factor.

Transforming growth factors (TGFs) were purified from serum-free medium conditioned by retrovirus-transformed Fisher rat embryo fibroblasts, mouse 3T3 cells, and two human melanoma cell lines. The purification of each TGF was monitored in a radioreceptor assay based on receptor crossreactivity with mouse submaxillary gland epidermal growth factor (mEGF) and was achieved by gel permeation chromatography of the acid-soluble TGF-containing activity, followed by reverse-phase high-pressure liquid chromatography with sequential use of acetonitrile and 1-propanol in the presence of aqueous trifluoroacetic acid. The amino-terminal sequences of rat, mouse, and human TGFs were determined. Extensive sequence homology was found among TGF polypeptides from different species and cell types. Alignment of the amino acid sequences of rat TGF, mEGF, and human urogastrone (hEGF) reveals statistically significant sequence homology. The reported results suggest that TGFs that compete for binding to the cellular EGF receptor and EGF may have evolved from a common progenitor.

Amino Acid Sequence↗
PubMed1983

Sarcoma growth factor from conditioned medium of virally transformed cells is composed of both type alpha and type beta transforming growth factors.

Sarcoma growth factor (SGF) derived from conditioned medium of Moloney sarcoma virus-transformed cells and partially purified by gel filtration (crude SGF) has been characterized by its ability both to compete with epidermal growth factor (EGF) for binding to membrane receptors and to induce anchorage-independent growth of untransformed cells. We now show that further purification of crude SGF by reverse-phase HPLC on muBondapak C18 and CN columns at pH 2 resolves it into two distinctly different polypeptides, which we call types alpha and beta transforming growth factors (TGFs). Type alpha TGF (TGF-alpha), but not type beta TGF (TGF-beta), competes for binding to the EGF receptor and induces the formation of small colonies (1,000-2,000 micron2) of normal rat kidney cells in soft agar. Both TGF-beta and EGF or TGF-alpha must be present in order to induce the formation of large colonies (7,000-15,000 micron2). Based on EGF competing equivalents as determined from a radioreceptor assay with 125I-labeled EGF in normal rat kidney cells, the relative ability of EGF and TGF-alpha to potentiate TGF-beta-dependent colony formation is in the order conditioned-medium TGF-alpha greater than EGF greater than intracellular TGF-alpha. Suboptimal concentrations of the same polypeptides give additive potentiation of the TGF-beta-dependent colony-forming response; saturating levels potentiate a similar maximum response whether used alone or in various combinations. The data indicate that the EGF-competing activity of crude SGF is due to its TGF-alpha component alone, whereas the soft-agar colony-forming activity is due to the combined action of two distinct polypeptides, TGF-alpha and TGF-beta.

Animals↗
PubMed1999

The transcription factor EGR-1 suppresses transformation of human fibrosarcoma HT1080 cells by coordinated induction of transforming growth factor-beta1, fibronectin, and plasminogen activator inhibitor-1.

Re-expression of EGR-1 in fibrosarcoma HT1080 suppresses transformation including tumorigenicity (Huang, R.-P., Liu, C., Fan, Y., Mercola, D., and Adamson, E. (1995) Cancer Res. 55, 5054-5062) owing in part to up-regulation of the transforming growth factor (TGF)-beta1 promoter by EGR-1 which suppresses growth by an autocrine mechanism (Liu, C., Adamson, E., and Mercola, D. (1996) Proc. Natl. Acad. Sci. U. S. A. 93, 11831-11836). Here we show that enhanced cell attachment contributes to the suppression via increased secretion of fibronectin (FN) and also of plasminogen activator inhibitor-1 (PAI-1). The secretion of FN and PAI-1 is strongly correlated with EGR-1 expression (RPEARSON = 0.971 and 0. 985, respectively). Addition of authentic TGF-beta1 to parental cells greatly stimulated secretion of PAI-1 but not FN, whereas addition of TGF-beta antibody or lipofection with specific antisense TGF-beta1 oligonucleotides to EGR-1-regulated cells completely inhibits the secretion of PAI-1 but not FN. However, in gel mobility shift assays pure EGR-1 or nuclear extracts of EGR-1-regulated cells specifically bind to two GC-rich elements of the human FN promoter at positions -75/-52 and -4/+18, indicating that the increased secretion of FN is likely due to direct up-regulation by EGR-1. Moreover, adhesion was greatly enhanced in EGR-1-regulated cells and was reversed by treatment with Arg-Gly-Asp (RGD) or PAI-1 antibody indicating that the secreted proteins are functional. We conclude that EGR-1 regulates the coordinated expression of gene products important for cell attachment ("oikis" factor) and normal growth control.

Cell Adhesion↗
PubMed1998

Chemotaxis of human keratocytes is increased by platelet-derived growth factor-BB, epidermal growth factor, transforming growth factor-alpha, acidic fibroblast growth factor, insulin-like growth factor-I, and transforming growth factor-beta.

PURPOSE: Following corneal wounding, early migration of keratocytes into the wound area is of pivotal importance in the healing process, but the nature of this migration is not well understood. The influence of peptide growth factors on the chemotactic and chemokinetic migration of human corneal keratocytes was investigated, using the following growth factors: platelet derived growth factor-BB (PDGF-BB), epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha), acidic fibroblast growth factor (aFGF), basic fibroblast growth factor (bFGF), insulin-like growth factor-I (IGF-I), and transforming growth factor-beta-1 (TGF-beta 1). METHODS: The chemotactic stimulation was investigated in the Boyden blind-well chemotaxis chamber, and the chemokinetic effect of the growth factors determined by a modified checker-board analysis. RESULTS: PDGF-BB, EGF and TGF-beta 1 stimulated chemotaxis towards a peak value, with a subsequent decline at higher concentrations. PDGF-BB and EGF peaked at 1 ng/ml with a 2.0 and a 2.5-fold increase respectively in the number of keratocytes migrating, whereas TGF-beta 1 reached a maximum response at 0.1 ng/ml, with a 1.7-fold increase. Chemotaxis reached an early plateau and remained constant at concentrations between 1 ng/ml and 100 ng/ml when stimulating with TGF-alpha (2.7-fold), bFGF (2.0-fold), aFGF (2.7-fold), and IGF-I (4.5-fold). Checkerboard analysis revealed that all growth factors were chemotactic agents for human keratocytes, except bFGF, which principally stimulated chemokinesis. CONCLUSION: These in vitro results demonstrate that PDGF-BB, EGF, TGF-alpha, aFGF, IGF-I, and TGF-beta 1 increase keratocyte chemotaxis, and they may play an important role in the early recruitment of keratocytes to the corneal wound site in vivo.

Becaplermin↗
PubMed1995

RRR-alpha-tocopheryl succinate inhibits DNA synthesis and enhances the production and secretion of biologically active transforming growth factor-beta by avian retrovirus-transformed lymphoid cells.

The RRR-alpha-tocopheryl succinate form of vitamin E, referred to as vitamin E succinate (VES), inhibits the proliferation of avian reticuloendotheliosis virus-transformed RECC-UTC4-1 (C4-1) lymphoblastoid cells in a dose-dependent manner in vitro. Analyses of conditioned medium (CM) from VES growth-inhibited cells revealed a potent antiproliferative activity. Characterization of the antiproliferative activity as transforming growth factor-beta (TGF-beta) was established by 1) growth inhibition of TGF-beta-responsive Mv1Lu mink lung and murine CTLL-2 cell lines, 2) a combination of physical characteristics including heat stability, acid stability, and Bio-Gel P-60 column chromatography elution profile, 3) neutralization of the antiproliferative activity by antibodies specific for TGF-beta, and 4) immunoprecipitation of metabolically labeled TGF-beta in CM from VES-treated C4-1 cells by use of TGF-beta-specific antibodies. Northern blot analyses of total cellular RNA revealed that VES does not alter the levels of constitutively expressed TGF-beta isoform-specific mRNAs; namely, VES does not alter the levels of the 3.9- and 4.1-kb TGF-beta 2 mRNAs, the 3.0-kb TGF-beta 3 mRNA, or the 2.5-, 2.7-, and 1.7-kb TGF-beta 4 mRNAs. The data show that VES inhibits C4-1 cell proliferation and induces the cells to produce and secrete active forms of TGF-beta, suggesting that one mechanism whereby VES inhibits C4-1 cell proliferation may be via the TGF-beta pathway for cellular growth control.

Animals↗
PubMed2002

Rapamycin potentiates transforming growth factor beta-induced growth arrest in nontransformed, oncogene-transformed, and human cancer cells.

Transforming growth factor beta (TGF-beta) induces cell cycle arrest of most nontransformed epithelial cell lines. In contrast, many human carcinomas are refractory to the growth-inhibitory effect of TGF-beta. TGF-beta overexpression inhibits tumorigenesis, and abolition of TGF-beta signaling accelerates tumorigenesis, suggesting that TGF-beta acts as a tumor suppressor in mouse models of cancer. A screen to identify agents that potentiate TGF-beta-induced growth arrest demonstrated that the potential anticancer agent rapamycin cooperated with TGF-beta to induce growth arrest in multiple cell lines. Rapamycin also augmented the ability of TGF-beta to inhibit the proliferation of E2F1-, c-Myc-, and (V12)H-Ras-transformed cells, even though these cells were insensitive to TGF-beta-mediated growth arrest in the absence of rapamycin. Rapamycin potentiation of TGF-beta-induced growth arrest could not be explained by increases in TGF-beta receptor levels or rapamycin-induced dissociation of FKBP12 from the TGF-beta type I receptor. Significantly, TGF-beta and rapamycin cooperated to induce growth inhibition of human carcinoma cells that are resistant to TGF-beta-induced growth arrest, and arrest correlated with a suppression of Cdk2 kinase activity. Inhibition of Cdk2 activity was associated with increased binding of p21 and p27 to Cdk2 and decreased phosphorylation of Cdk2 on Thr(160). Increased p21 and p27 binding to Cdk2 was accompanied by decreased p130, p107, and E2F4 binding to Cdk2. Together, these results indicate that rapamycin and TGF-beta cooperate to inhibit the proliferation of nontransformed cells and cancer cells by acting in concert to inhibit Cdk2 activity.

Animals↗
PubMed2000

Transforming growth factor-beta and breast cancer: Tumor promoting effects of transforming growth factor-beta.

The transforming growth factor (TGF)-betas are potent growth inhibitors of normal epithelial cells. In established tumor cell systems, however, the preponderant experimental evidence suggests that TGF-betas can foster tumor-host interactions that indirectly support the viability and/or progression of cancer cells. The timing of this 'TGF-beta switch' during the progressive transformation of epithelial cells is not clear. More recent evidence also suggests that autocrine TGF-beta signaling is operative in some tumor cells, and can also contribute to tumor invasiveness and metastases independent of an effect on nontumor cells. The dissociation of antiproliferative and matrix associated effects of autocrine TGF-beta signaling at a transcriptional level provides for a mechanism(s) by which cancer cells can selectively use this signaling pathway for tumor progression. Data in support of the cellular and molecular mechanisms by which TGF-beta signaling can accelerate the natural history of tumors will be reviewed in this section.

Breast Neoplasms↗
PubMed1999

IGF-I production by adult rat hepatocytes is stimulated by transforming growth factor-alpha and transforming growth factor-beta1.

Previously, we have observed that epidermal growth factor (EGF), a potent mitogen for cultured hepatocytes, stimulates the production of IGF-I and IGF-binding proteins (IGFBPs) by cultured hepatocytes from adult rats. This study was undertaken to investigate the possibility that other growth factors of hepatic origin could specifically be involved in the regulation of IGF-I and IGFBP expression. The effects of transforming growth factor-alpha (TGF-alpha), through EGF receptors to induce a mitogenic response, and transforming growth factor-beta1 (TGF-beta1), produced by non-parenchymal liver cells and able to inhibit hepatocyte proliferation in vivo and in culture, have been studied in cultured adult rat hepatocytes. Our results demonstrate that TGF-alpha and TGF-beta1 significantly stimulate IGF-I and IGFBP secretion by cultured hepatocytes but no change in the abundance of IGF-I and IGFBP mRNAs was observed with respect to controls. Cycloheximide is able to inhibit both basal and TGF-stimulated release of IGF-I and a similar effect was elicited by octreotide, the somatostatin analog, known to directly affect hepatic IGF-I gene expression. Our findings show the role of the liver in the secretion of IGF-I and IGFBPs, not only under endocrine and nutritional control but also under autocrine and paracrine control.

Animals↗
PubMed1997

The effects of basic fibroblast growth factor, transforming growth factor-alpha, and transforming growth factor-beta on mesenchymal cells in the rabbit phallus: an in-vitro study.

Effects of bFGF, TGFalpha and TGFbeta on cultured mesenchymal cells of rabbit phalli were investigated. A remarkable cell proliferation reaching confluency was only obtained from the media containing bFGF by the first week of culture. By subsequent 4 weeks culture using such confluent cells in the media containing bFGF, TGFalpha or TGFbeta, respectively, cells cultured in the media containing bFGF showed an active transformation to endothelial precursor cells determined by positive immunoreactions for factor VIII-related antigen at 2 weeks. By electron microscopy, such vasoformative cells appeared in contact with each other, occasionally forming a solid cell cord. The use of Matrigel's basement membrane matrix (Matrigel) in each culture bed promoted the capillary ingrowth, implying that certain extracellular matrix (ECM) components included in Matrigel may accelerate the formation of neocapillaries. Enhancement in the production of ECM components and transformation to smooth muscle cells determined by positive immunoreactions for actin were also seen in cells cultured in the media containing TGFalpha and TGFbeta, respectively. The present results indicate that the above growth factors play crucial roles in the differentiation of the rabbit cavernous body.

Animals↗
PubMed1989

Expression of mRNA for transforming growth factors-alpha and -beta and secretion of transforming growth factor-beta by renal cell carcinoma cell lines.

Transforming growth factors (TGFs)-alpha and -beta are regulatory polypeptides that reversibly confer a transformed phenotype upon normal cultured fibroblasts. TGF-alpha is synthesized primarily by malignant cells and shares many properties with the tissue mitogen, epidermal growth factor (EGF). The expression of TGF-beta mRNA has been demonstrated in a variety of normal and malignant cell types, some of which secrete the mature protein in an inactive form. To investigate the role of TGFs in human renal cell carcinoma (RCC), we used two renal tumor-derived cell lines and one established RCC cell line for analysis of TGF-alpha and TGF-beta mRNA production and for evaluation of TGF-beta protein secretion. By northern blot hybridization, all three RCC cell lines expressed TGF-alpha and -beta mRNA. In addition, TGF-beta activity was found in the conditioned medium from these cells. The secreted TGF-beta protein, however, displayed biological activity only after activation by acid-treatment. These data demonstrate the constitutive expression of TGF-alpha and -beta mRNA by RCC cell lines and, also, the secretion by this tumor of endogenous TGF-beta protein in a latent form.

Carcinoma, Renal Cell↗
PubMed1992

Differential regulation of transforming growth factor alpha autoinduction in a nontransformed and transformed epithelial cell.

Addition of transforming growth factor alpha (TGF-alpha) to cultured human keratinocytes results in enhanced expression of TGF-alpha mRNA. This phenomenon of TGF-alpha autoinduction is also observed in a TGF-alpha responsive colon cancer cell line, LIM 1215. In the present study, regulation of TGF-alpha autoinduction is examined in these two cell types. In human keratinocytes, but not in LIM 1215 cells, the increase in steady-state TGF-alpha mRNA following administration of TGF-alpha is due to stabilization of the 4.8-kilobase TGF-alpha transcript, as determined by actinomycin D decay curves. Nuclear run-on experiments confirmed transcriptional control in LIM 1215 cells. Basal and TGF-alpha-stimulated TGF-alpha expression is mediated, at least in part, through a protein kinase C-dependent pathway in both cell types, as determined by the protein kinase C inhibitor 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H7), which attenuates TGF-alpha mRNA accumulation. In the keratinocytes, but not in the LIM 1215 cells, basal TGF-alpha expression is mediated through an epidermal growth factor receptor-dependent pathway, as determined by antibody blockade of the epidermal growth factor receptor. Thus, differential regulation of TGF-alpha autoinduction exists in these nontransformed and transformed epithelial cell types.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1990

Inhibitory effects of transforming growth factor beta 1 on mitogenic response, transforming growth factor alpha, and c-myc in quiescent, well-differentiated colon carcinoma cells.

Previously, we reported that exponentially proliferating cultures of well-differentiated human colon carcinoma cells responded to transforming growth factor beta 1 (TGF-beta) with growth inhibition, alterations in morphology, and increased secretion of the differentiation marker, carcinoembryonic antigen. Poorly differentiated cultures were unresponsive. Here we show that TGF-beta was ineffective in repressing nutrient-stimulated mitogenesis in quiescent, poorly differentiated cells. However, in quiescent, well-differentiated cells, TGF-beta repressed the mitogenic responses to both nutrients alone (by 90%) and to nutrients plus the exogenous stimulatory factors epidermal growth factor (E), insulin (I), and transferrin (T) (by 55-65%). Thymidine incorporation experiments indicated that TGF-beta reduced both the onset and peak mitogenic response to growth factors and/or nutrients in the well-differentiated cells. Additionally, TGF-beta repressed the growth factor (E + I + T)-stimulated upregulation of expression of both c-myc and of transforming growth factor alpha (TGF-alpha) mRNAs in quiescent, well-differentiated cells. TGF-beta also elicited a rapid (t1/2 approximately 1h) down-regulation of c-myc expression in the absence of prior growth factor (E + I + T) stimulation. In contrast, TGF-beta had no effect on c-myc or TGF-alpha mRNA expression in the poorly differentiated cells. The results suggest that TGF-beta exerts rapid inhibitory effects on proliferation-associated genes in quiescent and restimulated, well-differentiated cells. Expression of these genes (c-myc and TGF-alpha) may otherwise (in the absence of TGF-beta) play roles in the cellular signaling of mitogenic responses by growth stimulatory factors in well-differentiated colon carcinoma cells.

Blotting, Northern↗
PubMed1986

Characterization of intra- and extracellular transforming growth factors from normal and avian sarcoma virus-transformed rat cells.

Intra- and extracellular transforming growth factors (TGFs) have been characterized in an avian sarcoma virus-transformed rat cell line, 77N1, and the nontransformed parental cell line, NRK. Serum-free conditioned medium from 77N1 and cell extracts from NRK and 77N1 were subjected to ion exchange column chromatography. Intracellular TGFs in cell extracts of NRK and 77N1 cells showed a major peak of DNA synthesis-stimulating and colony-forming activities which eluted in the 0.10 to 0.15 M salt concentration region. Extracellular TGF in conditioned medium of 77N1 cells showed a major peak of activity which eluted at 0.05 to 0.06 M salt concentration. Furthermore partially purified extracellular TGF had a molecular weight of about 40,000 daltons, whereas that for intracellular TGF was about 12,000 daltons. These intra- and extracellular TGFs, as well as TGF gamma 2 which was purified from 77N1 cell extract, were heat- and acid-labile polypeptides sensitive to treatment with dithiothreitol. Radioimmunoprecipitation analyses with antiserum against TGF gamma 2 demonstrated that intra- and extracellular TGFs in 77N1 and NRK cells were immunologically identical or very closely related to each other and suggested the possibility that extracellular TGF from 77N1 cells was released into serum-free conditioned medium after formation of complex with other cellular components.

Animals↗