Less frequent promoter hypermethylation of DLC-1 gene in primary breast cancers.
Absence or low expression of DLC-1, a tumor suppressor gene, in breast cancers has been shown recently. LOH of 8p12-p22, on which DLC-1 is located, is frequent in breast cancers, but the correlation between low expression of DLC-1 and LOH has not been confirmed. To determine the implication of aberrant methylation, one of the most frequent mechanisms of silencing the tumor suppressor or cancer-related genes, we examined the methylation status of DLC-1 promoter region in breast cancer cell lines and primary breast tumors. The hypermethylation status was examined by MSP and 25% of cell lines harbored a methylated allele. The gene silencing by methylation was also confirmed by the re-expression of DLC-1 by the 5-aza-2'-deoxycytidine treatment in DLC-1 hypermethylated cell line. But the methylation of DLC-1 gene was less frequently shown in primary breast cancers (10%). These data suggest that hypermethylation is responsible for silencing of DLC-1 gene in a limited portion of breast cancers.
Teramoto
Atsushi
A
Department of Cancer and Thoracic Surgery, Okayama University Graduate School of Medicine and Dentistry, Okayama 700-8558, Japan.
Tsukuda
Kazunori
K
Yano
Masaaki
M
Toyooka
Shinichi
S
Dote
Hideaki
H
Doihara
Hiroyoshi
H
Shimizu
Nobuyoshi
N
D000964:Antimetabolites, Antineoplastic / Q000633:toxicity; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000633:toxicity; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D045744:Cell Line, Tumor; D019175:DNA Methylation; D017931:DNA Primers; D004273:DNA, Neoplasm / Q000235:genetics*; D000077209:Decitabine; D005260:Female; D020690:GTPase-Activating Proteins; D005787:Gene Frequency; D020868:Gene Silencing; D006801:Humans; D009361:Neoplasm Invasiveness; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*
D000964:Antimetabolites, Antineoplastic; C112352:DLC1 protein, human; D017931:DNA Primers; D004273:DNA, Neoplasm; D020690:GTPase-Activating Proteins; D025521:Tumor Suppressor Proteins; D000077209:Decitabine; D001374:Azacitidine