title: Amphiregulin impairs apoptosis-stimulating protein 2 of p53 overexpression-induced apoptosis in hepatoma cells.
abstract: Overexpression of apoptosis-stimulating protein 2 of p53 (ASPP2) induces apoptotic cell death in hepatoma cells (e.g. HepG2 cells) by enhancing the transactivation activity of p53, but long-term ASPP2 overexpression fails to induce more apoptosis since activation of the epidermal growth factor/epidermal growth factor receptor/SOS1 pathway impairs the pro-apoptotic role of ASPP2. In this study, in recombinant adenovirus-ASPP2-infected HepG2 cells, ASPP2 overexpression induces amphiregulin expression in a p53-dependent manner. Although amphiregulin initially contributes to ASPP2-induced apoptosis, it eventually impairs the pro-apoptotic function of ASPP2 by activating the epidermal growth factor/epidermal growth factor receptor/SOS1 pathway, leading to apoptosis resistance. Moreover, blocking soluble amphiregulin with a neutralizing antibody also significantly increased apoptotic cell death of HepG2 cells due to treatment with methyl methanesulfonate, cisplatin, or a recombinant p53 adenovirus, suggesting that the function of amphiregulin involved in inhibiting apoptosis may be a common mechanism by which hepatoma cells escape from stimulus-induced apoptosis. Thus, our data elucidate an apoptosis-evasion mechanism in hepatocellular carcinoma and have potential implications for hepatocellular carcinoma therapy.
authors.affiliation: 1 Beijing Institute of Hepatology, Capital Medical University affiliated Beijing You An Hospital, Beijing, P.R. China.|2 Capital Medical University affiliated Beijing You An Hospital, Beijing, P.R. China.
authors.forename: Kai
authors.initials: K
authors.lastname: Liu
authors.affiliation: 2 Capital Medical University affiliated Beijing You An Hospital, Beijing, P.R. China.
authors.forename: Dongdong
authors.initials: D
authors.lastname: Lin
authors.affiliation: 1 Beijing Institute of Hepatology, Capital Medical University affiliated Beijing You An Hospital, Beijing, P.R. China.|2 Capital Medical University affiliated Beijing You An Hospital, Beijing, P.R. China.
authors.forename: Yabo
authors.initials: Y
authors.lastname: Ouyang
authors.affiliation: 1 Beijing Institute of Hepatology, Capital Medical University affiliated Beijing You An Hospital, Beijing, P.R. China.|2 Capital Medical University affiliated Beijing You An Hospital, Beijing, P.R. China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Pang
authors.affiliation: 1 Beijing Institute of Hepatology, Capital Medical University affiliated Beijing You An Hospital, Beijing, P.R. China.|2 Capital Medical University affiliated Beijing You An Hospital, Beijing, P.R. China.
authors.forename: Xianghua
authors.initials: X
authors.lastname: Guo
authors.affiliation: 1 Beijing Institute of Hepatology, Capital Medical University affiliated Beijing You An Hospital, Beijing, P.R. China.|2 Capital Medical University affiliated Beijing You An Hospital, Beijing, P.R. China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Wang
authors.affiliation: 2 Capital Medical University affiliated Beijing You An Hospital, Beijing, P.R. China.|3 Organ Transplantation Center, The Affiliated Hospital of Qingdao University, Qingdao, P.R. China.
authors.forename: Yunjin
authors.initials: Y
authors.lastname: Zang
authors.affiliation: 1 Beijing Institute of Hepatology, Capital Medical University affiliated Beijing You An Hospital, Beijing, P.R. China.|2 Capital Medical University affiliated Beijing You An Hospital, Beijing, P.R. China.|3 Organ Transplantation Center, The Affiliated Hospital of Qingdao University, Qingdao, P.R. China.
authors.forename: Dexi
authors.initials: D
authors.lastname: Chen
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D066258:Amphiregulin / Q000096:biosynthesis / Q000235:genetics*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D011994:Recombinant Proteins / Q000235:genetics; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D066258:Amphiregulin; D051017:Apoptosis Regulatory Proteins; D011994:Recombinant Proteins; C495901:TP53 protein, human; C090468:TP53BP2 protein, human; D016159:Tumor Suppressor Protein p53; D002945:Cisplatin
keywords: Amphiregulin; apoptosis; apoptosis-stimulating protein 2 of p53; hepatocellular carcinoma