Significance of Aurora B overexpression in hepatocellular carcinoma. Aurora B Overexpression in HCC
Journal
BMC Cancer
Journal Volume
10
Pages
461
Date Issued
2010
Author(s)
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. ? 2010 Lin et al; licensee BioMed Central Ltd.
SDGs
Other Subjects
2 [[3 [4 [5 [2 (3 fluoroanilino) 2 oxoethyl] 1h pyrazol 3 ylamino] 7 quinazolinyloxy]propyl](ethyl)amino]ethyl dihydrogen phosphate; aurora B kinase; beta catenin; messenger RNA; protein p53; AURKA protein, human; AURKB protein, human; beta catenin; messenger RNA; protein p53; protein serine threonine kinase; TP53 protein, human; tumor marker; adult; aged; antineoplastic activity; apoptosis; article; cancer cell culture; cancer grading; cancer invasion; cancer staging; cell cycle arrest; cell proliferation; controlled study; drug targeting; exon; female; gene interaction; gene location; gene mutation; gene overexpression; genetic analysis; genetic marker; human; human cell; human tissue; liver cell carcinoma; major clinical study; male; prognosis; protein dephosphorylation; reverse transcription polymerase chain reaction; tumor volume; adolescent; flow cytometry; follow up; genetics; liver tumor; metabolism; middle aged; mutation; pathology; tumor cell line; tumor recurrence; Western blotting; Adolescent; Adult; Aged; Aged, 80 and over; beta Catenin; Blotting, Western; Carcinoma, Hepatocellular; Cell Line, Tumor; Female; Flow Cytometry; Follow-Up Studies; Humans; Liver Neoplasms; Male; Middle Aged; Mutation; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Protein-Serine-Threonine Kinases; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Tumor Markers, Biological; Tumor Suppressor Protein p53; Young Adult
Type
journal article