Abstract 5361: Progesterone alters cell survival and cell death pathways in estrogen-induced mammary carcinogenesis

Abstract

Abstract Breast cancer is one of the most frequent and common malignancy in women. The incidence of breast cancer is high in postmenopausal women and majority of these cancers are estrogen receptor positive. Epidemiological data suggests that estrogen plus progesterone hormone replacement therapy increases the risk of breast cancer in postmenopausal women. Further, estrogen alone therapy did not increase the risk instead decreased the risk of breast cancer in postmenopausal women. Till date the role of progesterone in breast cancer is not well understood. Our earlier studies using ACI rats have clearly demonstrated the significant role progesterone plays in the estrogen-induced mammary carcinogenesis. We now, aim to investigate the mechanisms by which progesterone promotes estrogen-induced mammary carcinogenesis in ACI rats. We chose to use the ACI rats as it is a good model to study hormone-induced mammary carcinogenesis. In brief, seven weeks old female ACI rats were divided into the following groups: 1) untreated control, 2) rats treated with 30 mg estradiol, 3) rats treated with 30 mg progesterone, 4) rats treated with 30 mg estradiol plus 30 mg of mifepristone (a progesterone inhibitor). All hormone treatments were given for 30 days by subcutaneous implants of silastic capsules. At the end of the treatment, mammary glands were excised and used for molecular analysis. Cell survival, cell death pathways, and hormone receptor status were analyzed using different molecular techniques. Expression patterns of mRNA and proteins involved in major cell survival and apoptotic pathways were significantly altered in response to progesterone inhibition. Our data demonstrates that progesterone plays a prominent role in regulating key regulatory pathways in estrogen-induced mammary carcinogenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5361.