title: Estrogen-sensitive PTPRO expression represses hepatocellular carcinoma progression by control of STAT3.
abstract: Protein tyrosine phosphatase receptor type O (PTPRO), one of the receptor types of phosphotyrosine phosphatases (PTP), was recently described as a tumor suppressor in various kinds of cancers. We aimed to clarify the role of PTPRO in hepatocellular carcinoma (HCC). It was demonstrated in 180 pairs (120 male and 60 female) of clinical HCC specimens that the PTPRO level was significantly reduced, as compared with adjacent tissue, and the PTPRO level in male adjacent tissue was lower than in female. We further found that estrogen receptor alpha (ERα) could up-regulate PTPRO expression as a transcription factor. Moreover, an in vitro study showed that cell proliferation was inhibited and apoptosis was promoted in PTPRO-transduced HCC cell lines, whereas an in vivo study represented that tumor number and size was increased in ptpro(-/-) mice. As a result of its tumor-suppressive position, PTPRO was proved to down-regulate signal transducers and activators of transcription (STAT3) activity dependent on Janus kinase 2 (JAK2) and phosphoinositide 3-kinase (PI3K) dephosphorylation.
  
  
  CONCLUSIONS
  PTPRO expression results in pathological deficiency and gender bias in HCC, which could be attributed to ERα regulation. The suppressive role of PTPRO in HCC could be ascribed to STAT3 inactivation.
authors: Liver Transplantation Center of First Affiliated Hospital and State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China.
authors: Jiajie
authors: J
authors: Hou
authors: Juan
authors: J
authors: Xu
authors: Runqiu
authors: R
authors: Jiang
authors: Youjing
authors: Y
authors: Wang
authors: Chen
authors: C
authors: Chen
authors: Lei
authors: L
authors: Deng
authors: Xingxu
authors: X
authors: Huang
authors: Xuehao
authors: X
authors: Wang
authors: Beicheng
authors: B
authors: Sun
mesh_terms: D000818:Animals; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation; D004052:Diethylnitrosamine; D018450:Disease Progression; D015536:Down-Regulation; D047628:Estrogen Receptor alpha / Q000096:biosynthesis / Q000502:physiology*; D005260:Female; D006801:Humans; D053614:Janus Kinase 2 / Q000378:metabolism; D008113:Liver Neoplasms / Q000139:chemically induced / Q000378:metabolism; D008297:Male; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3 / Q000096:biosynthesis / Q000502:physiology*; D050796:STAT3 Transcription Factor / Q000235:genetics*; D012737:Sex Factors; D025521:Tumor Suppressor Proteins / Q000502:physiology
chemical_list: D047628:Estrogen Receptor alpha; D050796:STAT3 Transcription Factor; D025521:Tumor Suppressor Proteins; D004052:Diethylnitrosamine; D019869:Phosphatidylinositol 3-Kinases; D053614:Janus Kinase 2; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3