title: Klotho, an anti-senescence related gene, is frequently inactivated through promoter hypermethylation in colorectal cancer.
abstract: The potential anti-senescence gene Klotho (KL) has been recently found to participate in the progression of several different human cancers including breast, lung, and cervical cancer. In this current study, we identified KL as a candidate tumor suppressor gene silenced through promoter hypermethylation in colorectal cancer (CRC). KL gene expression is found to be absent or reduced in colon cancer cell lines (5/6, 83.3%), which can be reversed by treatment with demethylation agent 5-aza-2'-deoxycytidine (Aza), but not HDAC inhibitor trichostatin A. In addition, KL expression is markedly downregulated in colorectal carcinoma tissues when compared to the adjacent nontumor tissues (n=25, p<0.001). The methylation of the KL gene promoter was frequently detected in primary tumor tissues (34/40, 85%) when compared with adjacent nontumor colon tissues. Furthermore, ectopic expression of KL led to the cell proliferation inhibition of colon cancer cell lines via the induction of cell apoptosis and S-phase cell cycle arrest. Taken together, our results suggest that KL is inactivated through promoter hypermethylation and potentially functions as a tumor suppressor gene in CRC.
authors.affiliation: Department of Gastroenterology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Pan
authors.forename: Jing
authors.initials: J
authors.lastname: Zhong
authors.forename: Li Hong
authors.initials: LH
authors.lastname: Gan
authors.forename: Shu Jie
authors.initials: SJ
authors.lastname: Chen
authors.forename: Hong Chuan
authors.initials: HC
authors.lastname: Jin
authors.forename: Xian
authors.initials: X
authors.lastname: Wang
authors.forename: Liang Jing
authors.initials: LJ
authors.lastname: Wang
mesh_terms: D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation / Q000235:genetics*; D015536:Down-Regulation; D005260:Female; D020868:Gene Silencing; D016147:Genes, Tumor Suppressor; D005966:Glucuronidase / Q000235:genetics*; D006801:Humans; D000090265:Klotho Proteins; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011401:Promoter Regions, Genetic / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D005966:Glucuronidase; D000090265:Klotho Proteins