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.