DNA mismatch repair genes in renal cell carcinoma

Author(s): Deguchi M, Shiina H, Igawa M, Kaneuchi M, Nakajima K, et al.


Purpose: DNA mismatch repair is one of the correcting mechanisms that preserves genetic stability during replication or chemically induced damage. We hypothesized that genetic instability is due to a defect in mismatch repair genes in renal cell carcinoma. To test this hypothesis mismatch repair genes hMLH1, hMSH2, hMSH3, hMSH6, hPMS1 and hPMS2 were analyzed in renal cell carcinoma cell lines and tissues. We further investigated the mechanisms of inactivation of these genes through CpG methylation pathways.

Materials and methods: We analyzed 41 fresh normal and renal cell carcinoma samples for gene and protein expression of various mismatch repair genes (hMLH1, hMSH2, hMSH3, hMSH6, hPMS1 and hPMS2) using reverse transcriptase-polymerase chain reaction and immunohistochemistry techniques. To investigate the mechanisms of inactivation of these genes cultured renal cancer cell lines (A498, Caki-1 and Caki-2) were treated with demethylating agent (5-aza-2'-deoxycytidine), and mismatch repair genes and protein expression were analyzed before and after treatment.

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