title: Promoter methylation of TSLC1 and tumor suppression by its gene product in human prostate cancer.
abstract: 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.
authors.affiliation: Tumor Suppression & Functional Genomics Project, National Cancer Center Research Institute, Chuo-ku, Tokyo 104-0045.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Fukuhara
authors.forename: Masami
authors.initials: M
authors.lastname: Kuramochi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Fukami
authors.forename: Kohtaro
authors.initials: K
authors.lastname: Kasahara
authors.forename: Mutsuo
authors.initials: M
authors.lastname: Furuhata
authors.forename: Takahiro
authors.initials: T
authors.lastname: Nobukuni
authors.forename: Tomoko
authors.initials: T
authors.lastname: Maruyama
authors.forename: Kana
authors.initials: K
authors.lastname: Isogai
authors.forename: Takao
authors.initials: T
authors.lastname: Sekiya
authors.forename: Taro
authors.initials: T
authors.lastname: Shuin
authors.forename: Tadaichi
authors.initials: T
authors.lastname: Kitamura
authors.forename: Roger H
authors.initials: RH
authors.lastname: Reeves
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Murakami
mesh_terms: 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
chemical_list: 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