Promoter hypermethylation of DLC-1, a candidate tumor suppressor gene, in several common human cancers.
Aberrant methylation of CpG islands within the promoter regions of tumor suppressor or cancer-related genes is a common mechanism leading to the silencing of gene expression. To determine whether aberrant methylation is a contributing factor to transcriptional inactivation of DLC-1 (deleted in liver cancer-1), a candidate tumor suppressor gene, we examined its methylation status in twelve hepatocellular carcinoma. breast, colon, and prostate tumor cell lines with low or undetectable expression of DLC-1. By Southern blot analysis of DNA digested with the methylation sensitive enzyme HpaII, we found a different degree of promoter hypermethylation in all cell lines with aberrant DLC-1 expression. The hypermethylation status was reversed by the addition of 5-aza-2'-deoxycytidine, a demethylating agent, in one human hepatocellular carcinoma line. These observations suggest that hypermethylation is responsible for abrogating the function of the DLC-1 gene in a subset of liver, breast, colon, and prostate cancers.
Yuan
Bao-Zhu
BZ
Health Effects Laboratory Division, Toxicology and Molecular Biology Branch, National Institute for Occupational Safely and Health, Morgantown, WV 26505, USA.
Durkin
Marian E
ME
Popescu
Nicholas C
NC
D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000473:pathology; D003110:Colonic Neoplasms / Q000235:genetics / Q000473:pathology; D018899:CpG Islands; D019175:DNA Methylation / Q000187:drug effects; D004273:DNA, Neoplasm / Q000737:chemistry* / Q000235:genetics; D000077209:Decitabine; D005260:Female; D020690:GTPase-Activating Proteins; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D016147:Genes, Tumor Suppressor; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology; D008297:Male; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000172:deficiency / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology; D014407:Tumor Cells, Cultured / Q000737:chemistry / Q000473:pathology; D025521:Tumor Suppressor Proteins / Q000172:deficiency / Q000235:genetics*
C112352:DLC1 protein, human; D004273:DNA, Neoplasm; D020690:GTPase-Activating Proteins; D009363:Neoplasm Proteins; D025521:Tumor Suppressor Proteins; D000077209:Decitabine; D001374:Azacitidine