title: Reduced expression of Slit2 in renal cell carcinoma.
abstract: Slit2, initially identified as an important axon guidance molecule in the nervous system, was suggested to be involved in multiple cellular processes. Recently, Slit2 was reported to function as a potential tumor suppressor in diverse tumors. In this study, we systematically analyzed the expression level of Slit2 in renal cell carcinoma. Compared to paired adjacent non-malignant tissues, both Slit2 mRNA and protein expression were significantly down-regulated in renal cell carcinoma (RCC). Methylation-specific PCR showed that Slit2 promoter was methylated in two renal carcinoma cell lines. Pharmacologic demethylation dramatically induced Slit2 expression in cancer cell lines with weak expression of Slit2. Besides, bisulfite genomic sequencing confirmed that dense methylation existed in Slit2 promoter. Furthermore, in paired RCC samples, Slit2 methylation was observed in 8 out of 38 patients (21.1 %), which was well correlated with the down-regulation of Slit2 in RCC. Therefore, Slit2 may also be a potential tumor suppressor in RCC, which is down-regulated in RCC partially due to promoter methylation.
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Key Laboratory of Medical Immunology (Ministry of Health), Peking University Health Science Center, No. 38 Xueyuan Road, Beijing, 100191, China.
authors.forename: Wei-Jie
authors.initials: WJ
authors.lastname: Ma
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhou
authors.forename: Dan
authors.initials: D
authors.lastname: Lu
authors.forename: Dong
authors.initials: D
authors.lastname: Dong
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Tian
authors.forename: Jie-Xi
authors.initials: JX
authors.lastname: Wen
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000368:Aged; D001374:Azacitidine / Q000031:analogs & derivatives / Q000737:chemistry; D002292:Carcinoma, Renal Cell / Q000378:metabolism*; D045744:Cell Line, Tumor; D019175:DNA Methylation; D000077209:Decitabine; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D019169:Jurkat Cells; D007680:Kidney Neoplasms / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D000098552:Slit Homolog 2 Protein
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D000077209:Decitabine; D001374:Azacitidine; D000098552:Slit Homolog 2 Protein