Estrogen Sensitive PTPRO Expression Represses Hepatocellular Carcinoma Progression

Hepatocellular carcinoma(HCC) is a kind of malignant tumor which is the third leading reason of cancer-related death world widely. Therefore building the theoretical foundation for the development of cell signaling based new drugs and novel targets in treatment and prevention of HCC has became more and more important. Thus the study on anti-carcinogenesis and survival ability by liver cancer etiology is a feasible strategy for prevention of HCC.Tyrosine phosphatase receptor type O(PTPRO) is a phosphotyrosine phosphatase(PTP) receptor; recent studies have shown that PTPRO acts as a tumor suppressor in a variety of tumors. We found that, compared with clinical paraneoplastic tissues, PTPRO level was significantly lower in tumor tissue. At the same time, we also found that in male patients’ adjacent tissues, PTPRO level is much lower than the female patients. In further studies, we found that the estrogen receptor alpha(ERα) could raise the PTPRO expression as a transcription factor. Meanwhile, in vitro study, it showed that cell proliferation was suppressed and cell apoptosis was increased in the PTPRO transduced HCC cell lines. Similarly, in vivo study, tumor number and size in PTPRO knockout mouse were significantly increased. So, as a tumor suppressor, PTPRO was confirmed to down-regulate signal transduction and activator of transcription factor 3(STAT3) activity dependent of JAK2 and PI3 K dephosphorylation.In conclusion, the expression of PTPRO in HCC that shows the pathological deficiency and gender bias could be attributed to the regulation of ERα. And the role of PTPRO which suppressed HCC development could be attributed to the inhibition of STAT3 activation.