Mitogenic activity of steroidogenesis-inducing protein (SIP) during hypoxic stress of human ovarian carcinoma cells

Steroidogenesis-inducing protein (SIP) is a novel growth factor isolated fr om human ovarian follicular fluid. While the steroidogenic and mitogenic ef fects appear to be restricted towards gonadal cell types, we have recently demonstrated that SIP is also a potent mitogen for cell lines derived from ovarian surface epithelial carcinomas. Here, we demonstrate that SIP revers es hypoxia-induced cell proliferation arrest of the human ovarian carcinoma cell line SKA, as determined by flow cytometry and cell proliferation assa ys. Concomitant with this reversal of proliferation arrest is an increase i n expression of cyclins D and E and a reduction in expression of the cyclin -dependent kinase inhibitor p27, Pretreatment of hypoxic SKA cells with SIP is also shown to increase Taxol sensitivity of these cells by two-fold. Th ese studies further characterize the mitogenic activity of SLP at the molec ular level and suggest that this protein may be an effective biological res ponse modifier for ovarian carcinoma cells. (C) 1998 Elsevier Science Irela nd Ltd. All rights reserved.