DNA methylator and mismatch repair phenotypes are not mutually exclusive in colorectal cancer cell lines.
A potential link between DNA repair and de novo methylation of exogenous sequences in colorectal cancer cell lines suggested that cells deficient in mismatch repair (MMR-) had an increased ability to silence the introduced virus promoter by DNA methylation due to the presence of a methylator phenotype (MET+) (Lengauer et al., 1997a). We explored this relationship in more detail and found that although there was a clear difference in the abilities of MMR+ cells to express the viral promoter compared to their MMR- counterparts, this difference was not consistently explained by levels of methylation in the viral promoter. Furthermore, we were unable to distinguish differences between the levels of methylation of six endogenous known CpG islands or 100 random DNA fragments containing CCGG sites within the cells. No consistent differences between the abilities of the cells to methylate the CpG island in exon 2 of the p16 gene were observed after transient demethylation by 5-aza-2'-deoxycytidine nor in the levels of expression of three human methyltransferase enzymes. Our results do not therefore support the existence of mutually exclusive DNA methylation (MET) and DNA repair (MMR) phenotypes. Oncogene (2000) 19, 943 - 952.
Pao
M M
MM
Department of Biochemistry and Molecular Biology, USC/Norris Comprehensive Cancer Center, MS#73, 1441 Eastlake Ave., Los Angeles, California, CA 90033, USA.
Liang
G
G
Tsai
Y C
YC
Xiong
Z
Z
Laird
P W
PW
Jones
P A
PA
D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D020137:Base Pair Mismatch / Q000187:drug effects / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000096:biosynthesis / Q000378:metabolism; D011088:DNA Ligases / Q000172:deficiency; D019175:DNA Methylation / Q000187:drug effects; D000090205:DNA Methyltransferase 3A; D004260:DNA Repair / Q000187:drug effects / Q000235:genetics*; D000077209:Decitabine; D006801:Humans; D010641:Phenotype; D012190:Retroviridae / Q000235:genetics; D014407:Tumor Cells, Cultured; D000097584:DNA Methyltransferase 3B
D001374:Azacitidine; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; D011088:DNA Ligases; D000090205:DNA Methyltransferase 3A; D000077209:Decitabine; D000097584:DNA Methyltransferase 3B; C000717967:DNMT3A protein, human