Abstract 5362: Mechanisms involved in hormone promoted growth of preneoplastic mammary lesions

Abstract

Abstract Carcinogenesis is a complex process, which involves initiation, promotion and progression. Copenhagen strain of rat is a well known animal model which is resistant to carcinogen-induced mammary carcinogenesis. In our laboratory, we were able to induce a very high incidence of mammary cancers in these rats using combination of carcinogen N-methyl-N-nitrosourea (MNU), followed by estradiol and progesterone treatment. We have demonstrated that the resistance to mammary carcinogenesis in these rats is not due to inhibition of initiation but due to reduced hormone promotional environment and we further extend our research to investigate the molecular mechanisms involved behind this hormone-induced promotion. We used both in vivo and in vitro experimental system to understand the mechanisms involved in mammary cancer promotion and progression. Seven week old female Copenhagen rats were administered a single dose of MNU at a dose of 50 mg/kg body weight intraperitoneally. Four weeks post carcinogen administration, the rats were killed and preneoplastic lesions were excised and used for further in vitro experiments. The preneoplastic lesions were cultured and were treated with estradiol, progesterone or a combination of both hormones. Changes in survival and cell death pathways in the cultured preneoplastic lesions in response to different hormone treatments were analyzed using different molecular techniques. Our result indicates that hormone treatment induces alterations in cell survival and cell death pathways of the preneoplastic lesions demonstrating the significance of hormones in promotion and progression of breast cancer. 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 5362.