Calcium Signaling and Prostate Cancer

Major clinical problem with prostate cancer is the cell's ability to survive and proliferate upon androgen withdrawal. Indeed, deregulated cell proliferation together with the suppression of apoptosis provides the condition for abnormal tissue growth.Alterations in Ca2+ homeostasis have been described to increase proliferation, to induce differentiation or apoptosis. During the last years it has emerged that several members of the TRP family could play an important role in prostate carcinogenesis and even more, some of them have been suggested as a prognostic markers for PCa especially useful in the differential diagnosis.We were particularly interested by TRPM8 channels since TRPM8 is a target gene of the androgen receptor and its expression strongly increases in prostate cancer. Recent evidence we have obtained indicate that TRPM8 may be expressed not just in the plasma membrane, but also in the endoplasmic reticulum (ER) membrane where TRPM8 may operate as an ER Ca2+ release channel. The “preferred” TRPM8 localization depends on epithelial cell phenotype (differentiated apical cells vs. non-differentiated basal cells) and on androgen status (androgen-dependent vs. hormone refractory. New results on the differential physiological role of TRPM8 isoforms in prostate cancer cells will be presented.