title: Androgen activates PEG10 to promote carcinogenesis in hepatic cancer cells.
abstract: The molecular mechanism of striking higher prevalence of hepatocellular carcinoma (HCC) in male subjects has not yet been fully elucidated. Here, we report that androgen receptor (AR) is differentially expressed in different HCC cell lines. AR agonist dihydrotestosterone (DHT) enhances HCC cell growth and apoptotic resistance. Antagonist flutamide (FLU) blocks the effects of DHT on the HCC cell lines. Paternally expressed gene 10 (PEG10) is expressed in HCC cell lines at substantial high level. Using small interfering RNAs against AR and PEG10 in AR- and PEG10-expressing BEL-7404 hepatoma cells and HuH7 hepatoma cells (HuH7) cells, and AR-transfection technique in AR-lacking and PEG10-expressing HepG2 cells, we have confirmed that through upregulation and activation of PEG10, DHT enhances HCC cell growth and apoptotic resistance. We have further demonstrated that DHT upregulates expression of human telomerase reverse transcriptase (hTERT) in HCC cell lines in a PEG10-dependent manner. Moreover, AR directly interacts in vivo with androgen-responsive elements in the regions of promoter and exon 2 of PEG10 gene in HCC cell lines. DHT promotes the hepatoma formation in vivo nude mice through PEG10 activation. AR antagonists (FLU and valproate) inhibit the hepatoma formation. These findings suggest that PEG10 plays an essential role in hepatocarcinogenesis. The PEG10 inhibition can be a novel approach for therapy of HCC.
authors: Department of Immunology, and Laboratory of Allergy and Clinical Immunology, Institute of Allergy and Immune-related Diseases and Medical Research Center, Wuhan University School of Medicine, Wuhan, China.
authors: X
authors: X
authors: Jie
authors: C
authors: C
authors: Lang
authors: Q
authors: Q
authors: Jian
authors: L
authors: L
authors: Chaoqun
authors: Y
authors: Y
authors: Dehua
authors: S
authors: S
authors: Yi
authors: J
authors: J
authors: Yanping
authors: X
authors: X
authors: Luokun
authors: Z
authors: Z
authors: Qiuping
authors: W
authors: W
authors: Hui
authors: G
authors: G
authors: Feili
authors: J
authors: J
authors: Boquan
authors: J
authors: J
authors: Youxin
authors: T
authors: T
authors: Jinquan
mesh_terms: D000726:Androgen Antagonists / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D015152:Blotting, Northern; D015153:Blotting, Western; D002273:Carcinogens / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D047369:Chromatin Immunoprecipitation; D004268:DNA-Binding Proteins; D013196:Dihydrotestosterone / Q000494:pharmacology*; D005434:Flow Cytometry; D005485:Flutamide / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D011506:Proteins / Q000235:genetics*; D034741:RNA, Small Interfering / Q000494:pharmacology; D016601:RNA-Binding Proteins; D011944:Receptors, Androgen / Q000378:metabolism; D020218:Response Elements / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019098:Telomerase / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D000726:Androgen Antagonists; D051017:Apoptosis Regulatory Proteins; D002273:Carcinogens; D004268:DNA-Binding Proteins; C432965:PEG10 protein, human; D011506:Proteins; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D011944:Receptors, Androgen; D013196:Dihydrotestosterone; D005485:Flutamide; C509186:TERT protein, human; D019098:Telomerase