The functions of
activin, a member of
TGF-beta superfamily, in ovarian
clear cell adenocarcinoma remain unsolved, although we recently found that
inhibin betaA-subunit,
activin A,
activin receptor type IA, type IB, type IIA, type IIB, Smad2, Smad3 and Smad4 were localized in
tumor cells of the ovarian
clear cell adenocarcinoma tissue by immunohistochemistry. In the present study, in order to investigate the role of
activin concerning cell growth in ovarian
clear cell adenocarcinoma cells, we determined the production of
activin A and
inhibin A, and the expression of
activin receptors and Smads using the human ovarian
clear cell adenocarcinoma cell line JHOC-5. Moreover, we examined the effects of
activin A on the activation of
activin signaling pathway and on the proliferation in JHOC-5 cells. We detected a measurable amount of
activin A in the culture medium of JHOC-5 cells, although
inhibin A was not detected. The expression of
activin receptor type IA, IB, IIA, IIB, Smad2, Smad3 and Smad4 was observed in JHOC-5 cells.
Activin A induced a significant increase in proliferation of JHOC-5 cells compared with the untreated control. On the other hand,
activin A did not affect the growth of JHOC-5 cells and no statistically significant difference was observed in the presence of
follistatin which is a specific
binding protein of
activin. Phosphorylated Smad2, an activated form of Smad2, was detected both in treated JHOC-5 cells and in untreated cells by
activin A.
Activin A significantly increased the expression of phosphorylated Smad2 in JHOC-5 cells. Therefore, it is possible that
activin has autocrine roles in
tumor growth of ovarian
clear cell adenocarcinoma cells.