PNNL

Abstract

Although ovarian surface epithelial (OSE) cells are responsible for the majority of ovarian tumors, we know relatively little about the pathway(s) that are responsible for regulating their proliferation. We found that phosphatidylinositol 3-kinase (PI3K) is activated in OSE cells in response to elevated extracellular calcium, and the PI3K inhibitors wortmannin and LY29004 inhibited ERK activation by approximately 75%, similar to effects of the MEK2 inhibitor PD98059. However, in assays of proliferation we found that PD98059 inhibited proliferation by approximately 50%, while wortmannin inhibited greater than 90% of the proliferative response to elevated calcium. Expression of a dominant negative PI3K totally inhibited ERK activation in response to calcium. These results demonstrate that ERK activation cannot account for the full proliferative effect of elevated calcium in OSE cells, and suggest the presence of an ERK independent, PI3K dependant component in the proliferative response.