Estrogen Sensitive Protein Tyrosine Phosphatase Receptor Type-O Expressed In Hepatocellular Carcinoma

Objective: To investigate the expression and gender disparity of PTPRO (Proteintyrosine phosphatase receptor-type O) in human hepatocellular carcinoma（HCC）,and its correlation with recurrence after hepatectomy, whether PTPRO can serve as adesirable prognostic index;2. To determine the level of estrogen receptors in HCCand correlation with PTPRO, and understand the regulation of PTPRO level byestrogen signaling.Methods:1. PTPRO expression of HCC tissue, adjacent tissue in59male and22female patients were determined by Real-time PCR and immunohistochemistry（IHC）, as well as estrogen receptors(ERs);2. Gender disparity of PTPRO and ERsand the correlation between PTPRO and ERs were analyzed by t test, correlationanalysis and F test;3. The correlation between PTPRO level and recurrence ratepost-hepatectomy of HCC patients were analyzed by Kaplan-Meier curve andlog-rank test;4. ERα over-expression was realized via lentivirus mediatedtransduction in Huh-7-ERα and SMCC-7721-ERα, then variation of PTPRO wasdetermined by Real-time PCR and Western Blot;5. Promoter region of PTPRO wascloned and point mutation of ERE（Estrogen responsive element）was constructed viaPCR based method, and promoter activity was detected by luciferase reporter assay.Results:1. Expression of PTPRO and ERα in HCC tissues were significantly lowerthan adjacent cirrhotic tissues（P<0.01）;2. Expression of PTPRO and ERα in maleHCC adjacent tissue was lower than female（P<0.01）;3. Expression of PTPRO wasrelated to recurrence of HCC patients (P<0.001);4. Both mRNA and protein level of PTPRO was up-regulated in ERα transduced HCC cell lines;5. Promoter activitywas significantly decreased when EREs in promoter region were mutated.Conclusion:1. PTPRO level was significantly decreased in HCC, and representedgender disparity;2. PTPRO can serve as a candidate for both tumor suppressor andclinical prognostic index predicting recurrence;3. ERα reduced in HCC was able toup-regulate PTPRO level in a transcription factor manner, which may explaindown-regulation and gender disparity of PTPRO in HCC.