1. Significance of Aurora B overexpression in hepatocellular carcinoma. Aurora B Overexpression in HCC
- Author
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Zhong-Zhe Lin, Hung-Wei Pan, Ann-Lii Cheng, Hsin-Wei Tsao, Po-Lin Lai, Hey-Chi Hsu, Po-Huang Lee, Fu-Chang Hu, and Yung-Ming Jeng
- Subjects
Male ,Cancer Research ,medicine.disease_cause ,Exon ,Aurora Kinases ,Aurora Kinase B ,beta Catenin ,Aged, 80 and over ,Mutation ,Reverse Transcriptase Polymerase Chain Reaction ,Liver Neoplasms ,Cell cycle ,Middle Aged ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Flow Cytometry ,Oncology ,Hepatocellular carcinoma ,embryonic structures ,Female ,biological phenomena, cell phenomena, and immunity ,Research Article ,Adult ,Beta-catenin ,Carcinoma, Hepatocellular ,Adolescent ,Blotting, Western ,Aurora B kinase ,Biology ,Protein Serine-Threonine Kinases ,lcsh:RC254-282 ,Young Adult ,Cell Line, Tumor ,Genetics ,medicine ,Biomarkers, Tumor ,Humans ,Neoplasm Invasiveness ,RNA, Messenger ,Aged ,HCCS ,medicine.disease ,Molecular biology ,digestive system diseases ,enzymes and coenzymes (carbohydrates) ,biology.protein ,Neoplasm Recurrence, Local ,Tumor Suppressor Protein p53 ,Follow-Up Studies - Abstract
Background To investigate the significance of Aurora B expression in hepatocellular carcinoma (HCC). Methods The Aurora B and Aurora A mRNA level was measured in 160 HCCs and the paired nontumorous liver tissues by reverse transcription-polymerase chain reaction. Mutations of the p53 and β-catenin genes were analyzed in 134 and 150 tumors, respectively, by direct sequencing of exon 2 to exon 11 of p53 and exon 3 of β-catenin. Anticancer effects of AZD1152-HQPA, an Aurora B kinase selective inhibitor, were examined in Huh-7 and Hep3B cell lines. Results Aurora B was overexpressed in 98 (61%) of 160 HCCs and in all 7 HCC cell lines examined. The overexpression of Aurora B was associated with Aurora A overexpression (P = 0.0003) and p53 mutation (P = 0.002) and was inversely associated with β-catenin mutation (P = 0.002). Aurora B overexpression correlated with worse clinicopathologic characteristics. Multivariate analysis confirmed that Aurora B overexpression was an independent poor prognostic factor, despite its interaction with Aurora A overexpression and mutations of p53 and β-catenin. In Huh-7 and Hep3B cells, AZD1152-HQPA induced proliferation blockade, histone H3 (Ser10) dephosphorylation, cell cycle disturbance, and apoptosis. Conclusion Aurora B overexpression is an independent molecular marker predicting tumor invasiveness and poor prognosis of HCC. Aurora B kinase selective inhibitors are potential therapeutic agents for HCC treatment.
- Published
- 2010