Differential effects of CREB (cAMP responsive element binding) protein expression between normal ovarian surface epithelial cells and cell lines derived from ovarian cancers
O Gubbay1, MT Rae1, AJ Zeleznik2 & SG Hillier1
Approximately 90% of ovarian cancers are derived from ovarian surface epithelial (OSE) cells and are believed to result from repeated episodes of ovulation-associated injury and repair. A knowledge of the control of OSE cell survival is therefore of major interest regarding our understanding of ovarian cancers. We have previously demonstrated that CREB protein is activated in OSE cells around pre-ovulatory follicles and suggested that this activation may play a role to promote cell survival. In this study, the effect of adenoviral-mediated expression of wild-type and a dominant negative mutant (S133A) of CREB protein was investigated in cultures of OSE cells from four patients and four ovarian cancer cell lines (PEO4, PEO14, SKOV3 and BG1). Our data demonstrated that expression of mutant CREB protein induced apoptosis in normal OSE as evidenced by cellular morphology and caspase 3/7 activation (9 fold; p<0.05). Expression of mutant CREB protein, however, did not induce apoptosis in the cell lines derived from ovarian cancers. The induction of apoptosis by expression of mutant CREB protein was further shown to be suppressed in response to estrogen. We speculate that CREB, or CREB-associated, signalling is important to maintain OSE cell survival and is deficient in cells derived from ovarian cancer.