Transient receptor potential channel C3 contributes to the progression of human ovarian cancer.
Ovarian cancer (OC) is the leading cause of death from gynecological malignancy. However, the mechanism by which OC develops remains largely unknown. Increases in cytosolic free Ca(2+) ([Ca(2+)](i)) can result in different physiological changes including cell growth, differentiation and death. The transient receptor potential (TRP) C channels are nonselective cation channels with permeability to Ca(2+). Here we report that TRPC3 channels promote human OC growth. The TRPC3 protein levels in human OC specimens were greatly increased than those in normal ovarian specimens. Downregulating TRPC3 expression in SKOV3 cells, a human OC cell line, led to reduction of proliferation, suppression in epidermal growth factor-induced Ca(2+) influx, dephosphorylation of Cdc2 and CaMKIIalpha and prolonged progression through M phase of these cells. Further, decreased the expression of TRPC3 suppressed the tumor formation generated by injecting SKOV3 cells in nude mice. Together, our results suggest that increased activity of TRPC3 channels is necessary for the development of OCs.
Yang
S L
SL
Laboratory of Neural Signal Transduction, Institute of Neuroscience, Shanghai Institutes of Biological Sciences, State Key Laboratory of Neuroscience, Shanghai, China.
Cao
Q
Q
Zhou
K C
KC
Feng
Y J
YJ
Wang
Y Z
YZ
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002455:Cell Division; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018450:Disease Progression; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D010051:Ovarian Neoplasms / Q000209:etiology* / Q000473:pathology; D050052:TRPC Cation Channels / Q000032:analysis / Q000037:antagonists & inhibitors / Q000502:physiology*
D050052:TRPC Cation Channels; C104603:TRPC3 cation channel; D002118:Calcium