Promoter methylation of TSLC1 and tumor suppression by its gene product in human prostate cancer.
We recently identified TSLC1, a tumor suppressor gene in human lung cancer. Gene silencing by promoter methylation has been observed frequently in adenocarcinoma of the lung, liver, and pancreas. Here, we demonstrate that TSLC1 expression is also absent or markedly reduced in 3 of 4 prostate cancer cell lines. Promoter sequences of TSLC1 were heavily methylated in PPC-1 cells that lacked TSLC1 expression, supporting the idea that promoter methylation is strongly correlated with complete loss of gene expression. Promoter sequences of TSLC1 were also methylated significantly in 7 of 22 (32%) primary prostate cancers. Hypermethylation of the promoter occurred not only in advanced tumors, but also in relatively early-stage tumors. Restoration of TSLC1 expression substantially suppressed tumor formation of PPC-1 cells in nude mice. These findings indicate that alteration of TSLC1 is involved in prostate cancer.
Fukuhara
Hiroshi
H
Tumor Suppression & Functional Genomics Project, National Cancer Center Research Institute, Chuo-ku, Tokyo 104-0045.
Kuramochi
Masami
M
Fukami
Takeshi
T
Kasahara
Kohtaro
K
Furuhata
Mutsuo
M
Nobukuni
Takahiro
T
Maruyama
Tomoko
T
Isogai
Kana
K
Sekiya
Takao
T
Shuin
Taro
T
Kitamura
Tadaichi
T
Reeves
Roger H
RH
Murakami
Yoshinori
Y
D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules; D018899:CpG Islands; D019175:DNA Methylation; D020868:Gene Silencing; D006801:Humans; D007136:Immunoglobulins; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism; D011506:Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013447:Sulfites / Q000494:pharmacology; D013997:Time Factors; D025521:Tumor Suppressor Proteins
C403514:CADM1 protein, human; C498598:Cadm1 protein, mouse; D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; D008565:Membrane Proteins; D011506:Proteins; D013447:Sulfites; D025521:Tumor Suppressor Proteins; C042345:hydrogen sulfite