Persistent alteration of microRNA expression in hypothalamo-pituitary axis results in the reduction of breast cancer risk

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SAT 292-325-Breast & Prostate Cancer
Basic
Saturday, June 15, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SAT-302
Sushmita B Nandy*1, Arunkumar Arumugam1, Thiyagarajan Boopalan2, Rebecca Lopez3, Christina Gutierrez4 and Rajkumar Lakshmanaswamy5
1Texas Tech University Health Sci, El Paso, TX, 2Texas Tech Univ, El Paso, TX, 3Texas Tech University Health Sciences, El Paso, TX, 4Texas Tech University Health Sciences Center, El Paso, TX, 5Texas Tech Univ Health Sci Ctr, El Paso, TX
An early full-term pregnancy in women decreases the risk of breast cancer by fifty percent. This pregnancy-induced protection against breast cancer is also observed in rats and mice. Short-term treatment with pregnancy levels of estradiol mimics the protective effect of pregnancy against mammary carcinogenesis in rats and mice. The reason for pregnancy or short-term estradiol induced protection is not well defined.  We have earlier demonstrated persistent alterations in gene and protein expressions in the hypothalamus and pituitary of animals protected against breast cancer. The small non-coding microRNAs have been demonstrated to play a vital role in regulating gene expression. In the current study, we have investigated how and which microRNAs regulate the altered expression. Using the well-established rat chemical carcinogenesis model we have attempted to identify the persistent alterations in microRNA expressions between control rats that are highly susceptible to mammary carcinogenesis in comparison to rats that have undergone pregnancy or that have received the short-term estradiol treatment. Our preliminary results indicate that there are clear differences in the expression pattern of certain microRNAs ( miR 7, miR 218, miR429, miR 200b, miR 96) in the hypothalamus and pituitary of parous and short-term estradiol treated animals. Based on our results we have performed insilico analysis and have found the target genes of the altered microRNAs. We knocked down or over expressed the differentially expressed microRNAs in normal and breast cancer cell lines and have studied the impact altered expression of these microRNAs in mammary carcinogenesis. Overall, our results demonstrate that pregnancy and short-term estradiol treatment persistently alter microRNA expression in the hypothalamo-pituitary axis favoring inhibition of mammary carcinogenesis.

Nothing to Disclose: SBN, AA, TB, RL, CG, RL

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm