TRPM8 channels are highly expressed in prostate cancer cells but the physiological and pathological functions of TRPM8 in these cells are not known. In addition to prostate cancer (PC) cells, TRPM8 is expressed in sensory neurons where it acts as a sensor of cold. Recently, trpm8 has been identified as both an important gene regulated by androgens and a critical regulator of Ca2+ homeostasis. The androgen and its receptor (AR) are pivotal in the biology of sex hormone-regulated malignancies, with PC the most affected tumor. From the chromatin-immunoprecipitation (ChIP) analysis, we observed that an androgen response element (ARE) mediates androgen regulation of TRPM8. Further, using immunoprecipitation and calcium-imaging experiments, we identified that TRPM8 Ca+2 channels are functionally associated with androgens (testosterone and 5α-dihydrotestosterone) in the prostate. We also identified that unlike prostate cancer cell lines (LNCAP, PC3 and RWPE2) and normal prostate tissues, prostate tumor tissues (grade 1-4) showed high levels of TRPM8 which was predominantly localized as the plasma membrane protein at the tumor periphery. Of note, the decreased stabilization of TRPM8 on the plasma membrane was associated with increased expression of AR protein. These results suggest an important role of androgen signaling in trpm8 gene transcription corroborating to cancer progression and clinical lethality in prostate cancer.
Citation Format: Swapna Asuthkar, Kiran Velpula, Eleonora Zakharian. TRPM8 channel as a novel molecular target in androgen-regulated prostate cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 615. doi:10.1158/1538-7445.AM2014-615