title: Frequent amplification of PTP1B is associated with poor survival of gastric cancer patients.
abstract: The protein tyrosine phosphatase 1B (PTP1B), a non-transmembrane protein tyrosine phosphatase, has been implicated in gastric pathogenesis. Several lines of recent evidences have shown that PTP1B is highly amplified in breast and prostate cancers. The aim of this study was to investigate PTP1B amplification in gastric cancer and its association with poor prognosis of gastric cancer patients, and further determine the role of PTP1B in gastric tumorigenesis. Our data demonstrated that PTP1B was significantly up-regulated in gastric cancer tissues as compared with matched normal gastric tissues by using quantitative RT-PCR (qRT-PCR) assay. In addition, copy number analysis showed that PTP1B was amplified in 68/131 (51.9%) gastric cancer cases, whereas no amplification was found in the control subjects. Notably, PTP1B amplification was positively associated with its protein expression, and was significantly related to poor survival of gastric cancer patients. Knocking down PTP1B expression in gastric cancer cells significantly inhibited cell proliferation, colony formation, migration and invasion, and induced cell cycle arrested and apoptosis. Mechanically, PTP1B promotes gastric cancer cell proliferation, survival and invasiveness through modulating Src-related signaling pathways, such as Src/Ras/MAPK and Src/phosphatidylinositol-3-kinase (PI3K)/Akt pathways. Collectively, our data demonstrated frequent overexpression and amplification PTP1B in gastric cancer, and further determined the oncogenic role of PTP1B in gastric carcinogenesis. Importantly, PTP1B amplification predicts poor survival of gastric cancer patients.
authors.affiliation: a Department of Endocrinology ; The First Affiliated Hospital of Xi'an Jiaotong University School of Medicine ; Xi'an , People's Republic of China.
authors.forename: Na
authors.initials: N
authors.lastname: Wang
authors.forename: Junjun
authors.initials: J
authors.lastname: She
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Jing
authors.initials: J
authors.lastname: Shi
authors.forename: Qi
authors.initials: Q
authors.lastname: Yang
authors.forename: Bingyin
authors.initials: B
authors.lastname: Shi
authors.forename: Peng
authors.initials: P
authors.lastname: Hou
mesh_terms: D000368:Aged; D017209:Apoptosis / Q000235:genetics; D059447:Cell Cycle Checkpoints / Q000235:genetics; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D015536:Down-Regulation / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005260:Female; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D012333:RNA, Messenger; C516607:PTPN1 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1
keywords: Akt, serine/threonine protein kinase; DMEM, Dulbecco's modified Eagles medium; DMSO, dimethyl sulfoxide; EDTA, Ethylenediaminetetraacetic acid; EMT, epithelial-to-mesenchymal transition; Erk, elk-related tyrosine kinase; FAK, focal adhesion kinase; FITC, fluoresceine isothiocyanate; FOXO3a, Forkhead class O transcription factor 3a; Gastric cancer; H&E, hematoxylin and eosin; HR, hazard ratio; HRP, horseradish peroxidase; IHC, immunohistochemistry; MAPK, mitogen-activated protein kinase; MMPs, metalloproteinases; MTT, 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide; Mdm2, mouse double minute 2; PBS, phosphate buffered saline; PI3K, phosphatidylinositol 3-kinase; PTP1B; PTP1B, protein tyrosine phosphatase 1B; PVDF, polyvinylidene fluoride; RPMI 1640, Roswell Park Memorial Institute 1640; RT-PCR, Reverse-transcription polymerase chain reaction; SDS-PAGE, sodium dodecyl sulfate-polyacrylamide gel electrophoresis; genomic amplification; poor prognosis; siRNA, short interfering RNA.; signaling pathways