Menstrual cycle-dependent expressions of
activin A in normal human endometrial tissues have been reported. Expression of
activin receptor mRNAs and increased
activin A production were also observed in human endometrial
adenocarcinoma tissues, suggesting that
activin A might enhance cell proliferation and inhibit apoptotic signaling in
endometrial cancer cells. In this study, we have examined the effects of
activin A on cell proliferation, anticancer
drug-induced apoptosis and Fas-mediated apoptosis in 3 differentiated human endometrial
adenocarcinoma cell lines, namely HEC-1, HHUA and Ishikawa. Flow cytometric analyses revealed moderate expressions of all 4 types of
activin receptor subunits on the cell surfaces of the 3 cell lines. The proliferations of the 3
endometrial cancer cells were completely unaffected by
activin A, whereas it suppressed the cell proliferation of a human ovarian
endometrioid adenocarcinoma cell line, OVK-18, in a dose-dependent manner. Moreover,
activin A did not affect the apoptotic changes in the 3 endometrial
adenocarcinoma cells treated with 4 different anticancer drugs, namely CDDP,
paclitaxel,
etoposide and SN38. The apoptotic changes in HHUA cells treated with anti-Fas
IgM were also unaffected by
activin A. These results indicate that the increased
activin A production in human endometrial
adenocarcinoma tissues in vivo may not stimulate
carcinoma cell proliferation or inhibit apoptotic signaling in
carcinoma cells. Insensitivity to the usual growth suppression signals induced by
activin A might be one of the mechanisms of immortality of human endometrial
adenocarcinoma cells.