title: Prolactin promotes hepatocellular carcinoma through Janus kinase 2.
abstract: BACKGROUND
  Hepatocellular carcinoma (HCC) is one human cancer with obvious gender disparity. This study investigated the association of aberrant prolactin levels with HCC risk and the potential impacts on HCC of the prolactin receptor (PRLR)/Janus kinase 2 (JAK2) signaling.
  
  
  METHODS
  Serum prolactin of 63 HCC patients and 162 subjects without HCC was measured by radioimmunoassay. The expressions of PRLR and phosphorylated JAK2 (p-JAK2) in 82 retrospectively collected HCC specimens were evaluated by immunohistochemistry and further incorporated into the survival analysis. The immunoblotting and proliferation assays were used to analyze the effects of PRLR/JAK2 signaling on liver cancer cells with prolactin treatment.
  
  
  RESULTS
  Serum prolactin level was significantly higher in HCC patients than in controls. Hepatocellular carcinoma patients with high p-JAK2 expression had a significantly higher postoperative risk than those with low p-JAK2 expression. Moreover, results from the multivariate analysis indicated the prognostic role of p-JAK2 expression with respect to overall survival in HCC patients. In addition, the Kaplan-Meier survival curve showed that high p-JAK2 expression was associated with poor survival in HCC patients with high PRLR expression. The immunoblotting assay showed that prolactin induced the expression of both p-JAK2 and cyclin D1 in Hep-G2 cells. Importantly, the proliferative effects induced by prolactin could be effectively attenuated by adding AG490, a JAK2 inhibitor.
  
  
  CONCLUSIONS
  Increased circulating prolactin was found in HCC patients and high p-JAK2 expression could predict poor overall survival in those patients expressing high PRLR. In addition, prolactin contributed to the proliferation of liver cancer cells through PRLR/JAK2 signaling.
authors.affiliation: Department of Medical Laboratory Sciences and Biotechnology, Fooyin University, Kaohsiung, Taiwan.
authors.forename: Yao-Tsung
authors.initials: YT
authors.lastname: Yeh
authors.affiliation: Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: King-Teh
authors.initials: KT
authors.lastname: Lee
authors.affiliation: Department of Medical Laboratory Sciences and Biotechnology, Fooyin University, Kaohsiung, Taiwan.|Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Chia-Jung
authors.initials: CJ
authors.lastname: Tsai
authors.affiliation: Department of Medical Laboratory Sciences and Biotechnology, Fooyin University, Kaohsiung, Taiwan.|Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Yu-Jie
authors.initials: YJ
authors.lastname: Chen
authors.affiliation: Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. snwang@kmu.edu.tw.|Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. snwang@kmu.edu.tw.|Cancer Center, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Rd., Kaohsiung, Taiwan. snwang@kmu.edu.tw.
authors.forename: Shen-Nien
authors.initials: SN
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000401:mortality / Q000601:surgery; D016022:Case-Control Studies; D005260:Female; D056945:Hep G2 Cells; D006498:Hepatectomy; D006801:Humans; D015151:Immunoblotting; D053614:Janus Kinase 2 / Q000378:metabolism*; D008113:Liver Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000601:surgery; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D011388:Prolactin / Q000097:blood*; D011446:Prospective Studies; D011981:Receptors, Prolactin / Q000378:metabolism*; D012189:Retrospective Studies; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor; D011981:Receptors, Prolactin; D011388:Prolactin; D053614:Janus Kinase 2