title: Mutation analysis of the gene encoding the human mannose 6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2R) in human cell lines resistant to growth inhibition by transforming growth factor beta(1) (TGF-beta(1)).
abstract: The mannose 6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2R) is involved in activating the transforming growth factor beta(1) (TGF-beta(1)), an inhibitor of the cell proliferation, and limiting the insulin-like growth factor 2 mediated-growth stimulation. The M6P/IGF2R gene has been reported to be mutated and deleted in various cancers, and is a candidate tumor suppressor gene. We studied the genomic structure of the M6P/IGF2R gene and designed the intron primers to detect mutations in the M6P/IGF2R gene of genomic DNA samples. The M6P/IGF2R gene consists of 48 exons. The previously reported 23 mutations of the M6P/IGF2R gene in human cancers, liver, breast, and gastrointestinal tumors, are located in five exons, exon 27, 28, 31, 40, 48. Using the intron primers designed in this study, polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis, and direct sequencing, we performed an initial analysis of the complete coding sequences of the M6P/IGF2R gene in 21 human cell lines resistant to growth inhibition by TGF-beta(1). An adenine-to-guanine transition, resulting in an asparagine-to-serine amino acid substitution, was found in one lung adenocarcinoma cell line at exon 40 where the mutation has been previously reported in human cancers. This is the first report of a mutation of the M6P/IGF2R gene in lung tumor. These results indicated that the mutation in M6P/IGF2R may be involved in human lung cancinogenesis.
authors.affiliation: Fourth Department of Internal Medicine, Nippon Medical School, Main Hospital, 1-1-5 Sendagi Bunkyo-ku, Tokyo 113-8602, Japan. gemma_akihiko/med4@nms.ac.jp
authors.forename: A
authors.initials: A
authors.lastname: Gemma
authors.forename: Y
authors.initials: Y
authors.lastname: Hosoya
authors.forename: K
authors.initials: K
authors.lastname: Uematsu
authors.forename: M
authors.initials: M
authors.lastname: Seike
authors.forename: F
authors.initials: F
authors.lastname: Kurimoto
authors.forename: A
authors.initials: A
authors.lastname: Yoshimura
authors.forename: M
authors.initials: M
authors.lastname: Shibuya
authors.forename: S
authors.initials: S
authors.lastname: Kudoh
mesh_terms: D002460:Cell Line; D004252:DNA Mutational Analysis; D017931:DNA Primers; D004273:DNA, Neoplasm / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005091:Exons; D015894:Genome, Human; D006801:Humans; D007438:Introns; D009154:Mutation; D016133:Polymerase Chain Reaction; D017527:Receptor, IGF Type 2 / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1; D014407:Tumor Cells, Cultured
chemical_list: D017931:DNA Primers; D004273:DNA, Neoplasm; D017527:Receptor, IGF Type 2; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1