Abstract 4160: miR-34a as a radio sensitizer of triple negative breast cancer.

Abstract

Abstract Introduction: Triple negative breast cancer (TNBC) is known to be relatively resistant to radiation therapy resulting in a comparatively higher rates of locoregional recurrence compared with non-TNBC patients. The mechanisms behind this relative radio resistance remain unknown. The goal of this study is to investigate the role of three miRNAs namely, miR-34a, miR-21, and miR-210, which are implicated in DNA damage-repair process, in the response of TNBC cell lines to radiation therapy. Methods: Seven TNBC breast cancer cell lines were used for the study. The levels of miR-34a, miR-21 and miR-210 were evaluated by taqman- based quantitative PCR assay. These cells were exposed to 2 Gy radiation dose and colonogenic survival was assessed after about 2 weeks. Survival fraction after 2 Gy (SF2), which is the ratio of number of cell colonies formed after 2 Gy radiation vs. the number of cell colonies with out radiation, was determined. The SF2 factor is a reliable index to measure radio sensitivity, greater the SF2 factor more radio resistant the cells are. Results: The SF2 value of the TNBC cells varied from 0.31 to 0.74 with MDA-MB-468, HCC-70 being the most radio sensitive cell lines and MDA-MB-436, BT-20 being the most radio resistant cell lines. MDA-MB- 231, BT-549 and Hs 578T were found to be moderately radio resistant breast cancer lines. The oncomiR -21 expression levels in these 7 TNBC cell lines varied from 0.85 to 4.18 fold with a very poor correlation with SF2 (r2=0.08). The oncomiR 210 levels varied from 0.49 to 9.19 fold and also did not exhibit any correlation with radio resistance in TNBC cells (r2= 0.141). Whereas the tumor suppressor miR, miR-34a expression showed an inverse correlation with radio resistance (r2=0.8) in TNBC cells. The radio resistant cell line (e.g., MDA-MB-436, SF2 = 0.74) expressed significantly low levels of miR-34a (0.016 fold) relative to miR -34a levels (set as 1) in HCC 70, which was found to be a radiosensitive cell line with SF2 of 0.309. Conclusions: Our preliminary data indicates that miR 34a may play a role in the response of TNBC cells to radiotherapy. Citation Format: Anjana Bhardwaj, Nivetha Ganesan, David Molkentine, Uma Raju, Isabelle Bedrosian. miR-34a as a radio sensitizer of triple negative 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 4160. doi:10.1158/1538-7445.AM2013-4160