Novel role for the transient receptor potential channel TRPM2 in prostate cancer cell proliferation.
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.
Zeng
X
X
Department of Urology, Tulane University Health Sciences Center, New Orleans, LA, USA.
Sikka
S C
SC
Huang
L
L
Sun
C
C
Xu
C
C
Jia
D
D
Abdel-Mageed
A B
AB
Pottle
J E
JE
Taylor
J T
JT
Li
M
M
D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D003593:Cytoplasm / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D008297:Male; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011470:Prostatic Hyperplasia / Q000503:physiopathology; D011471:Prostatic Neoplasms / Q000473:pathology / Q000503:physiopathology*; D034741:RNA, Small Interfering / Q000378:metabolism; D050053:TRPM Cation Channels / Q000502:physiology*
D034741:RNA, Small Interfering; D050053:TRPM Cation Channels; C121934:TRPM2 protein, human; D011065:Poly(ADP-ribose) Polymerases