title: Critical role of TRPC6 channels in the development of human renal cell carcinoma.
abstract: Renal cell carcinoma (RCC) is the most common tumor arising from the cells in the lining of tubules in the kidney. Some members of the Ca2+-permeable transient receptor potential canonical (TRPC) family of channel proteins have demonstrated a role in the proliferation of some types of cancer cells. In this study, we investigated the role of TRPC6 in the development of human RCC. RT-PCR and Western blotting were used to investigate TRPC6 expression in 1932 and ACHN cells. Immunohistochemical techniques were applied to study TRPC6 expression in 60 cases of RCC primary tissue samples and 10 cases of corresponding normal renal tissues. To inhibit TRPC6 activity or expression, RNA interference was used. The effects of TRPC6 channels on RCC cell viability and cell cycle progression were investigated by MTT and flow cytometry. TRPC6 was expressed in 1932 and ACHN cells. TRPC6 protein was detected in 73.3% of RCC samples, and there was a significant difference compared with the normal renal samples (30%) (p<0.05). Moreover the level of TRPC6 expression was associated with RCC Fuhrman grade (p<0.01). Blockade of TRPC6 channels in ACHN cells suppressed basal cell proliferation and partially inhibited HGF-induced cell proliferation. Furthermore, inhibition of TRPC6 channels expression prolonged the transition through G2/M phase in ACHN cells. In summary, expression of TRPC6 is markedly increased in RCC specimens and associated with RCC histological grade. TRPC6 plays an important role in ACHN cells proliferation.
authors.affiliation: School of Laboratory Medicine, Tianjin Medical University, Tianjin, 300203, China.
authors.forename: Jiayin
authors.initials: J
authors.lastname: Song
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.forename: Xue
authors.initials: X
authors.lastname: Li
authors.forename: Yanna
authors.initials: Y
authors.lastname: Shen
authors.forename: Meilin
authors.initials: M
authors.lastname: Yin
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Guo
authors.forename: Lei
authors.initials: L
authors.lastname: Diao
authors.forename: Yunde
authors.initials: Y
authors.lastname: Liu
authors.forename: Dan
authors.initials: D
authors.lastname: Yue
mesh_terms: D015153:Blotting, Western; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000503:physiopathology; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics / Q000502:physiology; D017931:DNA Primers / Q000235:genetics; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050052:TRPC Cation Channels / Q000378:metabolism*; D000074287:TRPC6 Cation Channel; D013778:Tetrazolium Salts; D013844:Thiazoles
chemical_list: D017931:DNA Primers; D050052:TRPC Cation Channels; D000074287:TRPC6 Cation Channel; C117032:TRPC6 protein, human; D013778:Tetrazolium Salts; D013844:Thiazoles; C022616:thiazolyl blue