DNA methylation and genetic instability in colorectal cancer cells.
Apparent alterations in DNA methylation have been observed in many cancers, but whether such alterations represent a persistent alteration in the normal methylation process is not known. In this study, we report a striking difference in the expression of exogenously introduced retroviral genes in various colorectal cancer cell lines. Extinguished expression was associated with DNA methylation and could be reversed by treatment with the demethylating agent 5-azacytidine. A striking correlation between genetic instability and methylation capacity suggested that methylation abnormalities may play a role in chromosome segregation processes in cancer cells.
Lengauer
C
C
Howard Hughes Medical Institute at The Johns Hopkins Oncology Center, Baltimore, MD 21231, USA.
Kinzler
K W
KW
Vogelstein
B
B
D001374:Azacitidine / Q000494:pharmacology; D001483:Base Sequence; D002460:Cell Line; D015179:Colorectal Neoplasms / Q000235:genetics*; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D005814:Genes, Viral; D006801:Humans; D019868:Kanamycin Kinase; D008969:Molecular Sequence Data; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000096:biosynthesis; D016133:Polymerase Chain Reaction; D014176:Protein Biosynthesis; D011994:Recombinant Proteins / Q000096:biosynthesis; D012091:Repetitive Sequences, Nucleic Acid; D012190:Retroviridae / Q000235:genetics; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured; D001616:beta-Galactosidase / Q000096:biosynthesis
D004273:DNA, Neoplasm; D011994:Recombinant Proteins; D017853:Phosphotransferases (Alcohol Group Acceptor); D019868:Kanamycin Kinase; D001616:beta-Galactosidase; D001374:Azacitidine