Abstract 5011: Molecular alterations in mammary stem cells in response to pregnancy or short-term estradiol treatment leads to the reduced risk of breast cancer.

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Breast cancer is the most common cancer in women worldwide. Early pregnancy is the only known natural phenomenon that reduces the risk of breast cancer. Rodents like rats and mice that undergo a full term pregnancy also have a greatly reduced susceptibility to chemical carcinogen induced mammary carcinogenesis compared to nulliparous rats and mice. Earlier we have demonstrated that short-term treatment with pregnancy levels of estradiol is highly effective in conferring protection against mammary carcinogenesis. Carcinogenesis is a multistep process which includes initiation, promotion and progression. In the current study our objective was to determine the molecular mechanisms underlying the protective effect conferred by parity and short-term treatment with pregnancy levels of estradiol against mammary carcinogenesis. We mainly focused on the differences in mammary stem cells between virgin, parous and short-term estradiol treated groups. Virgin Lewis rats were implanted with Alzet mini pumps releasing 1 microgram of estradiol/day at 7 weeks of age. The Alzet pumps were removed 3 weeks later. Rats were mated between 6-7 weeks of age. The pups and mother were weaned after three weeks of lactation. Six weeks after weaning or withdrawal of hormone treatment (16 weeks of age), the rats were treated with 50 mg/kg of N-methyl-N-nitorosurea (MNU). Rats from all the three groups were euthanized at different timepoints. Mammary gland was surgically removed and mammary stem cells were sorted using flow cytometry. Cells that were positive for aldehyde dehydrogenase, CD44 and low or negative for CD24 were sorted and used for molecular analysis. Using stem cell signaling PCR arrays we have attempted to identify differences in gene expression among mammary stem cells obtained from the three groups of animals. We observed clear differences in expression of fibroblast growth factor receptos (FGFRs), notch, smads, and transcription factors between virgin mammary stem cells in comparison to parous and short-term estratiol treated mammary stem cells. These findings are currently being validated using quantitative RTPCR and immunoblotting. The results obtained will be presented. The current data indicates that there are molecular differences in the mammary stem cells between animals that are susceptible to mammary carcinogenesis compared to animals that are protected against mammary carcinogenesis. Citation Format: Sushmita B. Nandy, Arunkumar Arumugam, Jacqueline Parada, Rebecca Lopez, Thiyagarajan Boopalan, Christina Gutierrez, Pamela Agullo, Rajkumar Lakshmanaswamy. Molecular alterations in mammary stem cells in response to pregnancy or short-term estradiol treatment leads to the reduced risk of breast cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5011. doi:10.1158/1538-7445.AM2013-5011