Androgen regulated TRPM8 expression: a potential mRNA marker for metastatic prostate cancer detection in body fluids

Abstract

Identification of sensitive and specific biomarkers for early detection and prognosis of prostate cancer is essential for timely and appropriate treatment of the disease in individual patients. We identified an RNA transcript with sequence homology to TRPM8 (melastatin-related transient receptor potential member 8) that was overexpressed in tumor vs. patient-matched non-tumor prostate tissues by RT-PCR differential display (DD). Semi-quantitative RT-PCR analysis revealed that TRPM8 levels were higher in tumor than in non-tumor tissue from 31 of 40 (>75%) patients examined. Overexpression of TRPM8 was independent of changes in androgen receptor (AR) mRNA levels in tumor tissue. However, in studies with established cell lines, TRPM8 expression was detectable only in AR-positive, but not in AR-negative cells, and it was suppressed by steroid deprivation or anti-androgen bicalutamide (Casodex) treatment, suggesting the requirement of AR activity for TRPM8 expression in prostate cancer cells. TRPM8 mRNA was also detected in body fluids of men. Most importantly, its levels were significantly higher (p<0.001, n=18) in urine and blood of patients with metastatic disease than in those of healthy men. However, there was no significant difference (p>0.05, n=10) in its levels between prostate cancer patients with localized disease and healthy men. Together, these studies demonstrate that TRPM8 expression is androgen regulated in prostate cancer cells and that, while tissue TRPM8 mRNA levels can be used for detection of prostate cancer, urine and blood TRPM8 mRNA levels may prove to be useful for distinguishing metastatic disease from clinically localized prostate cancer at the time of diagnosis.