Role of transforming growth factor beta in ovarian surface epithelium biology and ovarian cancer.

Ovarian cancers arise out of the ovarian surface epithelium (OSE), which is the single layer of epithelial cells covering the ovary. These cells go through repeated cycles of proliferation with the growth and rupture of ovarian follicles. One growth factor involved in the regulation of OSE is transforming growth factor beta (TGFbeta). The different isoforms of TGFbeta (TGFbeta1, TGFbeta2 and TGFbeta3) and its receptor are all present in both OSE and the underlying ovarian surface stroma. The levels of the TGFbeta isoforms and receptors are regulated independently of each other in these different ovarian tissues. Observations suggest the existence of multiple autocrine/paracrine TGFbeta signalling loops. TGFbeta acts to inhibit proliferation of normal OSE and early stage ovarian carcinomas. Conversely, in later stage ovarian cancer the inhibitory actions of TGFbeta on epithelial proliferation have been overcome, while TGFbeta is able to promote malignant neoplastic behaviours. The regulation of TGFbeta signalling by ovarian steroid hormones may be one mechanism by which the OSE responds to cyclic changes in the underlying follicles.