Abstract 1317: Estradiol and progesterone promotes breast tumor growth through induction of AKT/mTOR pathway and inhibition of apoptosis

Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL Breast cancer development is accomplished by unbalanced regulation of several signaling pathways. Studies indentifying potential targets for mammary cancer treatment and prevention are vital. 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. In the present study, we exposed 7 week old female Copenhagen rats to N-methyl-N-nitrosourea (MNU; 50mg/kg body weight). Immediately after MNU treatment the rats were divided into the following groups: 1) Control 2) 17β-estradiol (30mg) 3) progesterone (30mg) and 4) 17β-estradiol (30mg) plus progesterone (30mg). All hormone treatments were administered via individual silastic pellets for a period of 9 months post carcinogen treatment. At the end of the treatment period rat mammary tumors were excised and used for molecular analysis. Quantitative RT-PCR and western blot analysis showed that ovarian hormones treatment triggered the AKT/mTOR pathway along with increased cell cycle progression. Intra cellular MAPK signaling was increased through activation of AKT/PI3K pathway. Hormone administration decreased the levels of caspase-3, caspase-8 and caspase-9. Together, our result indicates that hormone treatment induces mammary tumor growth through activation of AKT/PI3K/mTOR pathways and simultaneously inhibiting apoptosis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1317. doi:10.1158/1538-7445.AM2011-1317