Promoter methylation status and expression of TMS1 gene in human epithelial ovarian cancer.
Gene silencing associated with aberrant DNA methylation of promoter CpG islands is one mechanism through which tumor suppressor genes are inactivated in human cancers. TMS1 (target of methylation-induced silencing) is a CpG island-associated gene that functions in the regulation of apoptosis. In this study, we examined the DNA methylation status of the TMS1 promoter in ovarian cancer cell lines and tissues by methylation-specific PCR (MSP) and its mRNA expression by reverse transcription and quantitative PCR. Aberrant methylation of TMS1 was present in 7/12 ovarian cancer cell lines and 8/20 primary ovarian cancer tissues. The median value of relative TMS1 gene expression in cancers with methylation (0.15) was significantly lower than that in cancers without methylation (13.9) (P < 0.001). The expression of the TMS1 gene was relatively high (48.5) in the normal ovarian cDNA library. TMS1 gene expression was restored by treatment with the demethylating agent 5-aza-2'-deoxycitidine in the OV90 cell line, which lacks the TMS1 transcript. Our results suggest that aberrant methylation of TMS1 may play a role in the pathogenesis of ovarian cancer.
Akahira
Jun-ichi
J
Department of Obstetrics and Gynecology, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai 980-8574, Japan. jakahira@ob-gy.med.tohoku.ac.jp
Sugihashi
Youko
Y
Ito
Kiyoshi
K
Niikura
Hitoshi
H
Okamura
Kunihiro
K
Yaegashi
Nobuo
N
D053468:CARD Signaling Adaptor Proteins; D045744:Cell Line, Tumor; D018899:CpG Islands / Q000235:genetics; D003598:Cytoskeletal Proteins; D019175:DNA Methylation; D005260:Female; D020868:Gene Silencing; D006801:Humans; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000502:physiology*; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D053468:CARD Signaling Adaptor Proteins; D003598:Cytoskeletal Proteins; C402202:PYCARD protein, human; D011506:Proteins; D012333:RNA, Messenger