title: Aberrant methylation and loss of CADM2 tumor suppressor expression is associated with human renal cell carcinoma tumor progression.
abstract: Cell adhesion molecules (CADMs) comprise a protein family whose functions include maintenance of cell polarity and tumor suppression. In this report, we show that the CADM2 gene is repressed in human clear renal cell carcinoma by DNA promoter hypermethylation and/or loss of heterozygosity. Moreover, the loss of CADM2 expression is associated with a higher tumor pathology stage (p<0.05). The re-expression of CADM2 in the renal cancer cell line 786-O significantly suppressed tumor cell growth in vitro and in mouse xenografts by a G1 phase cell cycle arrest and the induction of apoptosis. Lentivirus-mediated CADM2 expression also significantly suppressed cancer cell anchorage-independent growth and invasion. Furthermore, the inhibition of endogenous CADM2 expression using siRNAs induced a tumorigenic phenotype in polarized non-tumorigenic MDCK cells. Thus, we conclude that CADM2 functions as a novel tumor suppressor and may serve as a potential therapeutic target for human renal cell carcinoma.
authors: Department of Urology, Peking University First Hospital and the Institute of Urology, Peking University, No. 8, Xishiku Street, Xicheng District, Beijing 100034, China.
authors: Wei
authors: W
authors: He
authors: Xuesong
authors: X
authors: Li
authors: Shuping
authors: S
authors: Xu
authors: Junkui
authors: J
authors: Ai
authors: Yanqing
authors: Y
authors: Gong
authors: Jennifer L
authors: JL
authors: Gregg
authors: Ruili
authors: R
authors: Guan
authors: Wei
authors: W
authors: Qiu
authors: Dianqi
authors: D
authors: Xin
authors: Jeffrey R
authors: JR
authors: Gingrich
authors: Yinglu
authors: Y
authors: Guo
authors: Guimin
authors: G
authors: Chang
mesh_terms: D000818:Animals; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000473:pathology*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019175:DNA Methylation / Q000235:genetics*; D015536:Down-Regulation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C
chemical_list: C556123:CADM2 protein, human; D015815:Cell Adhesion Molecules