Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04626 (erbB-2)
 5,251 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In an attempt to understand the antiproliferative effects of progestins in endometrial cancer, we have examined the effects of the potent progestin, medroxyprogesterone acetate (MPA), on the cell proliferation and the expression of transforming growth factor (TGF) alpha and beta genes in human endometrial adenocarcinoma cell lines. The two cell lines used were Ishikawa, var 1, and HEC-50. In addition, the effects of exogenous TGF-alpha and anti-epidermal growth factor (EGF) receptor monoclonal antibody on cell proliferation were determined. Incubation of both cell lines with MPA resulted in a time- and dose-dependent inhibition of cell proliferation. Half-maximal growth inhibition was observed at 0.6 nM. In Ishikawa cells, the relative abundance of TGF-alpha was significantly reduced by MPA. A significant decrease in TGF-alpha mRNA was apparent 6 h after exposure to MPA and a further decrease was seen 12-24 h after addition of the progestin. The concentration of TGF-alpha immunoreactivity in conditioned medium of MPA-treated cells was also significantly reduced compared to control cultures. MPA had no effect on TGF-alpha expression by HEC-50 cells. EGF mRNA was not detected by Northern blot analysis in either cell type. MPA had no significant effect on EGF receptor mRNA abundance but resulted in a small increase in EGF receptor number in Ishikawa cells. Anti-EGF receptor monoclonal antibody (0.6-6 nM) inhibited Ishikawa cell growth but had no effect on HEC-50 cell proliferation. Exogenous TGF-alpha stimulated proliferation of both cell lines, but Ishikawa cells were significantly more sensitive to exogenous TGF-alpha than HEC-50 cells. Furthermore, TGF-alpha could reverse the growth inhibitory effects of MPA on Ishikawa cells. A decrease in TGF-beta mRNA abundance was also observed in MPA-treated Ishikawa and HEC-50 cells. This effect was of small magnitude, variable, and only observed after prolonged exposure to MPA. These observations are consistent with the hypothesis that the antiproliferative effects of progestins on Ishikawa cells are mediated by decreased expression and autocrine action of TGF-alpha. Since similar growth inhibition is also seen in the HEC-50 cells in which progestins have no effect on TGF-alpha expression, additional mechanisms are likely to be involved in the antiproliferative effects of progestins in human endometrial cancer.
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PMID:Transforming growth factor gene expression in human endometrial adenocarcinoma cells: regulation by progestins. 183 51

The role of estrogen and estrogen-related growth factors in the mechanism of hormone dependency of endometrial adenocarcinoma cells was investigated. The proliferation of hormone-responsive human endometrial adenocarcinoma cells (Ishikawa cells), which possess both estrogen and progesterone receptors, was optimally stimulated by 10 nM estradiol. Both transforming growth factor (TGF)-alpha and epidermal growth factor (EGF), added to the culture media, stimulated the proliferation of Ishikawa cells in a dose-dependent manner. Anti-TGF-alpha antibody completely eliminated the stimulatory effects of TGF-alpha. Anti-EGF receptor antibody inhibited the proliferation of these cells. The production of TGF-alpha into culture media was 5-40 pg/10 cells/24 h in 9 human endometrial adenocarcinoma cells. Ten nanomoles of estradiol increased the TGF-alpha production of Ishikawa cells by approximately 2.5-fold of the control level. In contrast, the production of TGF-alpha in hormone-unresponsive HEC-50 cels was not influenced by estradiol. C-erbB-2 oncoprotein expression of human endometrial adenocarcinoma cells, detected by both immunocytochemical staining and Western blot analysis, was associated with the tumor grade of the original tumor tissues. Ten nanomoles of estradiol clearly increased the c-erbB-2 oncoprotein levels at an optimal incubation period of 72 h, whereas estradiol did not affect the expression in HEC-50 cells.
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PMID:Role of estrogen and estrogen-related growth factor in the mechanism of hormone dependency of endometrial carcinoma cells. 985