Chlorinated pesticides such as beta-hexachlorocyclohexane (a-HCH) and heptachlor epoxide have been proposed as risks factor for breast, endometrial and ovarian cancers. Their mechanisms of action may be due to their ability to mimic the effects of estrogen and thus, produce such effects as cell proliferation and down regulation of estrogen receptors which are associated with phenotypical markers of carcinogenesis. These pesticides, however, do not have agonistic properties toward estrogen receptors and thus, must exert their activity through some other mechanisms including a """"""""ligand-independent"""""""" activation (LIA) mechanism similar to """"""""crosstalk"""""""" patterns seen between growth factor receptors and estrogen receptors. Therefore, the main goals of this project are to establish the existence """"""""ligand independent"""""""" activation mechanism for various chlorinated pesticides in our cell systems (BG-1 ovarian cancer cells, and Ishikawa endometrial cells). Secondly, experiments will be designed to dissect this LIA pathway for pesticides by investigating the molecular mechanisms which may be involved. This will be accomplished through the comparisons of the ability of chlorinated pesticide and established growth factor and cellular messenger activators to achieve LIA in the presence of possible LIA inhibitors (antibodies, second messenger inhibitors etc).
