Abstract 4951: 2-Methoxyestradiol (2-ME 2 ) induces microRNA alterations in prostate cancer cells: Role for miRs in 2-ME 2 -induced biological effects

Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL Prostate cancer is the second most common cause of death related to cancer in Western societies. 2-Methoxyestradiol (2-ME2), an endogenous metabolite of 17-β estradiol inhibits tumor cell proliferation in various cancer cells, including the prostate. Previous studies from our laboratory showed that 2-ME2 (i) inhibits proliferation of both androgen responsive and independent cells through induction of apoptosis involving G2/M check point block; (ii) prevents the development of prostate tumors in transgenic adenocarcinoma of mouse prostate (TRAMP) model. Although various molecular targets have been proposed, the mechanism of action behind its antiproliferative activity is still uncertain. Here we investigated the possible role for 2-ME2 induced antiproliferative activity by examining the altered regulation of microRNA (miRNAs). MicroRNAs are small non-coding RNAs that down regulate gene expression during cellular processes including proliferation and apoptosis. We compared the microRNA profile in non-tumorigenic (RWPE-1), androgen responsive (LNCaP) and androgen independent (PC-3) cells in response to 2-ME2 treatment in the presence and absence of androgen-stimulation (only in LNCaP cells) using the stem-loop RT-PCR based Taqman® Array Human MicroRNA Cards (Array A and B) representing 754 unique assays specific to human mature miRNAs (Applied Biosystems, Foster City, CA). Analysis of these data identified expression of only 50% of miRs in prostate cancer cells. About 26% and 12% of these are upregulated; 20.5% and 26% were down regulated in LNCaP and PC-3 cells respectively. However androgen stimulation of LNCaP cells resulted in upregulation of 34.2% and 15% down regulation of miRs whereas 2-ME2 treatment down regulated 28.7% of miRs. Target transcripts for these miRs have been identified. To the best of our knowledge this is the first study to report in-depth investigation of global miR changes in response to 2-ME2 induced biological effects. These data demonstrate that 2-ME2 suppresses proliferation and induces apoptosis in prostate cancer cells through modulation of microRNA signature. Supported by NIH CA 135451 (APK). 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 4951. doi:10.1158/1538-7445.AM2011-4951