Methylation-associated silencing of the Wnt antagonist SFRP1 gene in human ovarian cancers.
The SFRP1 gene on chromosome 8p11.2 encodes a Wnt signaling antagonist, and was recently demonstrated to be a new tumor suppressor that is inactivated by promoter methylation in human colon cancers. Here, we analyzed promoter methylation of the SFRP1 gene in human ovarian cancers, in which loss of heterozygosity in 8p is frequently observed and involvement of the Wnt signaling pathway has been suggested. Methylation-specific PCR (MSP) analysis showed that four of 13 ovarian cancer cell lines and two of 17 primary ovarian cancers had methylated SFRP1, while an immortalized ovarian epithelial cell line, HOSE, and seven ovarian endometrial cyst samples did not. In the four ovarian cancer cell lines with the methylation, SFRP1 was not expressed at all as determined by quantitative RT-PCR analysis. A cell line with SFRP1 methylation, MCAS, was treated with a demethylating agent, 5-aza-2'-deoxycytidine, and demethylation of the promoter and re-expression of SFRP1 were observed. These results show that SFRP1 is inactivated by promoter methylation in human ovarian cancers, as well as colon cancers.
Carcinogenesis Division, National Cancer Center Hospital, Chuo-ku, Tokyo 104-0045, Japan.
Toshio
T
Takada
Yukiko
Y
Yagi
Takao
T
Maekita
Masayoshi
M
Imura
Shunsuke
S
Nakagawa
Sai-Wah
SW
Tsao
Kazuaki
K
Miyamoto
Osamu
O
Yoshino
Toshiharu
T
Yasugi
Yuji
Y
Taketani
Toshikazu
T
Ushijima
D000328:Adult; D000368:Aged; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors; D000077209:Decitabine; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051153:Wnt Proteins; D000094742:Secreted Frizzled-Related Proteins
D001374:Azacitidine; D015254:DNA Modification Methylases; D000077209:Decitabine; D004791:Enzyme Inhibitors; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D051153:Wnt Proteins; C117636:SFRP1 protein, human; D000094742:Secreted Frizzled-Related Proteins