Suppression of the transformed phenotype and induction of differentiation-like characteristics in cultured ovarian tumor cells by chronic treatment with progesterone

Epidemiological evidence suggests that elevated levels of the pregnancy hormone progesterone might play a role in the reduced risk of women to develop ovarian cancer. In vitro studies have supported this hypothesis by demonstrating negative effects of this hormone on the growth and proliferation of cultured ovarian carcinoma cells. However, little is known about the underlying molecular processes and how progesterone might decrease the risk for ovarian tumors. Therefore, we investigated the effects of chronic hormone treatment on the cell-cycle and transformed phenotype of ovarian carcinoma cell lines in vitro. We found that long-term treatment of these cells with progesterone caused a concomitant reduction of cyclin-dependent kinase (CDK) activity. In parallel, these cells lost their transformed phenotype as indicated by the acquisition of contact inhibition and the loss of anchorage-independence, as well as the reduced expression of tumor markers such as heat shock protein (HSP) 72 and carcinoma antigen (CA) 125. In addition, progesterone-treated cells exhibited characteristics that resembled a more differentiated phenotype. Taken together, our data indicated that progesterone was able to suppress the transformed phenotype of ovarian tumor cells. This observation could serve to explain progesterone's alleged protective effect in ovarian carcinogenesis. (C) 2003 Wiley-Liss, Inc.