Novel role for the transient receptor potential channel TRPM2 in prostate cancer cell proliferation

• Published in: Prostate cancer and prostatic diseases Vol. 13; no. 2; pp. 195 - 201
• Main Authors: Zeng, X, Sikka, S C, Huang, L, Sun, C, Xu, C, Jia, D, Abdel-Mageed, A B, Pottle, J E, Taylor, J T, Li, M
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-06-2010; Nature Publishing Group
• Subjects: Biomedical and Life Sciences; Biomedicine; Cancer Research; Cell Membrane - metabolism; Cell Nucleus - metabolism; Cell proliferation; Cell Proliferation - drug effects; Cell receptors; Cytoplasm - metabolism; Development and progression; Gene Expression; Humans; Male; Original; original-article; Physiological aspects; Poly(ADP-ribose) Polymerases - metabolism; Prostate cancer; Prostatic Hyperplasia - physiopathology; Prostatic Neoplasms - pathology; Prostatic Neoplasms - physiopathology; RNA, Small Interfering - metabolism; TRPM Cation Channels - physiology; United States; TRPM2; siRNA; PARP; proliferation
• ISSN: 1365-7852; 1476-5608
• DOI: 10.1038/pcan.2009.55

We have identified a novel function for a member of the transient receptor potential (TRP) protein super-family, TRPM2, in prostate cancer cell proliferation. TRPM2 encodes a non-selective cation-permeable ion channel. We found that selectively knocking down TRPM2 with the small interfering RNA technique inhibited the growth of prostate cancer cells but not of non-cancerous cells. The subcellular localization of this protein is also remarkably different between cancerous and non-cancerous cells. In BPH-1 (benign), TRPM2 protein is homogenously located near the plasma membrane and in the cytoplasm, whereas in the cancerous cells (PC-3 and DU-145), a significant amount of the TRPM2 protein is located in the nuclei in a clustered pattern. Furthermore, we have found that TRPM2 inhibited nuclear ADP-ribosylation in prostate cancer cells. However, TRPM2 knockdown-induced inhibition of proliferation is independent of the activity of poly(ADP-ribose) polymerases. We conclude that TRPM2 is essential for prostate cancer cell proliferation and may be a potential target for the selective treatment of prostate cancer.