Expression Of FOXC1 In Clear Cell Renal Cell Carcinoma And Its Influence On Cell Proliferation And Cell Cycle

Objective:FOXC1, a transcription factor in superfamily of FOX, exerts various functions in many types of cancers. However, its role is not clear on clear cell renal cell carcinoma [2] which is the most common subtype in renal cell carcinoma. This study is to investigate the expression of FOXC1 on the tissue of ccRCC and adjacent normal tissues, the specific role of FOXC1 on cell proliferation and cell cycle, to establishe a basis for further study on the mechanism of FOXC1 affecting the origin and development of ccRCC.Materials and Methods:1.We collected 60 clear cell renal cell carcinoma [2] tissue samples and their corresponding adjacent normal tissue samples and then choosed real time PCR, western blot and immunofluorescence staining to detect the change expression of FOXC1 on mRNA and protein levels.2.Real time PCR and western-blot assay were used to detect the expression of FOXC1 on mRNA and protein levels in normal renal cell lines(HKC,HK2) and ccRCC cell lines(769-P,786-O, caki-1, OSRC-2).3.Overexpression and knockdown of FOXC 1 were generated in ccRCC cell lines to exert colony-forming assay, cell cycle assays and MTS for detecting cell proliferation.Results:1.The expression of FOXC1 was significantly lower in rumor group than in noncancerous tissue group on both mRNA and protein levels(both p<0.05) in 60 pairs surgical samples.2.Cell cycle assay showed a decreased G1 phase and increased S phase rate in the FOXC1 knock-down cell lines(p<0.05). Consistent with cell cycle assay, MTS and colony-forming assay also showed a higher growth rate in the FOXC1 knock-down ccRCC cell lines(both p<0.05).3.Overexpression of FOXC1 protein inhibited the cell proliferation(MTS), lowered the number of colony forming and arrested the cell cycle in G1 phase in ccRCC cell lines (p<0.05 respectively).Conclusions:The absence or low expression of FOXC1 commonly exists in ccRCC, and correlates with TNM stages. Downregulation of FOXC 1 promotes cancer cell proliferation and colony forming, oppositely, upregulation of FOXC 1 inhibits tumor malignancy. These result suggested the role of FOXC1 as a major tumor suppressor gene in ccRCC.