title: Induction of mutant p53-dependent apoptosis in human hepatocellular carcinoma by targeting stress protein mortalin.
abstract: Stress protein mortalin (mtHSP70) is highly expressed in cancer cells. It was shown to contribute to carcinogenesis by sequestrating the wild type p53, a key tumor suppressor protein, in the cytoplasm resulting in an abrogation of its transcriptional activation function. We have found that the level of mortalin expression has significant correlation with human hepatocellular carcinoma (HCC) malignancy and therefore investigated whether it interacts with and influences the activities of mutant p53, frequently associated with HCC development. We have detected mortalin-p53 interactions in liver tumor and five HCC cell lines that harbored mutant p53. The data was in contrast to the normal liver and immortalized normal hepatocytes that lacked mortalin-p53 interaction. Furthermore, we have found that the shRNA-mediated mortalin silencing could induce mutant p53-mediated tumor-specific apoptosis in HCC. Such allotment of apoptotic function to mutant p53 by targeting mortalin-p53 interaction in cancer cells is a promising strategy for HCC therapy.
authors.affiliation: Department of Surgery, The University of Hong Kong, Pokfulam, Hong Kong, China.
authors.forename: Wen-Jing
authors.initials: WJ
authors.lastname: Lu
authors.forename: Nikki P
authors.initials: NP
authors.lastname: Lee
authors.forename: Sunil C
authors.initials: SC
authors.lastname: Kaul
authors.forename: Feng
authors.initials: F
authors.lastname: Lan
authors.forename: Ronnie T P
authors.initials: RT
authors.lastname: Poon
authors.forename: Renu
authors.initials: R
authors.lastname: Wadhwa
authors.forename: John M
authors.initials: JM
authors.lastname: Luk
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D045744:Cell Line, Tumor; D016158:Genes, p53; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics*; D009154:Mutation; D034741:RNA, Small Interfering / Q000494:pharmacology
chemical_list: D018840:HSP70 Heat-Shock Proteins; D034741:RNA, Small Interfering; C080352:mortalin