Role of estrogen and estrogen-related growth factor in the mechanism of hormone dependency of endometrial carcinoma cells

The role of estrogen and estrogen-related growth factors in the mechanism o f hormone dependency of endometrial adenocarcinoma cells was investigated. The proliferation of hormone-responsive human endometrial adenocarcinoma ce lls (Ishikawa cells), which possess both estrogen and progesterone receptor s, was optimally stimulated by 10 nM estradiol. Both transforming growth fa ctor (TGF)-alpha and epidermal growth factor (EGF), added to the culture me dia, stimulated the proliferation of Ishikawa cells in a dose-dependent man ner. Anti-TGF-alpha antibody completely eliminated the stimulatory effects of TGF-alpha. Anti-EGF receptor antibody inhibited the proliferation of the se cells. The production of TGF-alpha into culture media was 5-40 pg/10 cel ls/24 h in 9 human endometrial adenocarcinoma cells. Ten nanomoles of estra diol 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 associat ed with the tumor grade of the original tumor tissues. Ten nanomoles of est radiol clearly increased the c-erbB-2 oncoprotein levels at an optimal incu bation period of 72 h, whereas estradiol did not affect the expression in H EC-50 cells.