title: Cell Transformation by PTP1B Truncated Mutants Found in Human Colon and Thyroid Tumors.
abstract: Expression of wild-type protein tyrosine phosphatase (PTP) 1B may act either as a tumor suppressor by dysregulation of protein tyrosine kinases or a tumor promoter through Src dephosphorylation at Y527 in human breast cancer cells. To explore whether mutated PTP1B is involved in human carcinogenesis, we have sequenced PTP1B cDNAs from human tumors and found splice mutations in ~20% of colon and thyroid tumors. The PTP1BΔE6 mutant expressed in these two tumor types and another PTP1BΔE5 mutant expressed in colon tumor were studied in more detail. Although PTP1BΔE6 revealed no phosphatase activity compared with wild-type PTP1B and the PTP1BΔE5 mutant, its expression induced oncogenic transformation of rat fibroblasts without Src activation, indicating that it involved signaling pathways independent of Src. The transformed cells were tumourigenic in nude mice, suggesting that the PTP1BΔE6 affected other molecule(s) in the human tumors. These observations may provide a novel therapeutic target for colon and thyroid cancer.
authors.affiliation: Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory of Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai, 200025, China.
authors.forename: Wenhan
authors.initials: W
authors.lastname: Mei
authors.affiliation: Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory of Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai, 200025, China.
authors.forename: Kemin
authors.initials: K
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory of Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai, 200025, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY, United States of America.
authors.forename: Xinmin
authors.initials: X
authors.lastname: Zheng
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000378:metabolism* / Q000473:pathology*; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D004789:Enzyme Activation; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D050505:Mutant Proteins / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D010766:Phosphorylation; D020033:Protein Isoforms / Q000378:metabolism; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000378:metabolism*; D051381:Rats; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D015398:Signal Transduction; D013964:Thyroid Neoplasms / Q000378:metabolism* / Q000473:pathology*; D014410:Tumor Stem Cell Assay; D014443:Tyrosine / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D050505:Mutant Proteins; D020033:Protein Isoforms; D014443:Tyrosine; D017526:Receptor, IGF Type 1; D019061:src-Family Kinases; C516607:PTPN1 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1