Significance of Aurora B overexpression in hepatocellular carcinoma. Aurora B Overexpression in HCC

Abstract

BackgroundTo investigate the significance of Aurora B expression in hepatocellular carcinoma (HCC).MethodsThe 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.ResultsAurora 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.ConclusionAurora 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.

CHK2 overexpression and mislocalisation within mitotic structures enhances chromosomal instability and hepatocellular carcinoma progression

“…Moreover, Chk2 localisation to the kinetochores and midbody region suggests that Chk2 may directly affect spindle assembly function, similar to Aurora B kinase,42 but only when DNA damage exists. The data obtained in this study fit a model whereby abnormal expression of Chk2 and Aurora B kinase disrupts the sensitive balance of mitotic proteins, which in turn undermines faithful chromosome segregation 34. If the relative expression levels of the proteins involved in the quality control of the machinery which ensures chromosome segregation fidelity is disrupted by mitotic errors and DNA damage, the resulting imbalance could further compromise chromosome segregation accuracy.…”

Aurora B Is Regulated by the Mitogen-activated Protein Kinase/Extracellular Signal-regulated Kinase (MAPK/ERK) Signaling Pathway and Is a Valuable Potential Target in Melanoma Cells

“…Given their function in the control of the G 2 /M phase, the expression of the chromosomal passenger protein complex proteins is controlled in a cell cycle-dependent manner. However, in-creased expression of some of these components such as Aurora B and Survivin has been observed in a spectrum of cancers, including melanoma (5,6), and predicts early tumor recurrence and poor prognosis (7,8).…”

Regulation of AURKC expression by CpG island methylation in human cancer cells

“…Three members of Aurora kinase family, Aurora-A, Aurora-B, and Aurora-C (AURKA, AURKB, AURKC) share conserved catalytic domain while their N-terminal domains have variable sequence and length [2,3]. Deregulated overexpression of AURKA and AURKB, implicated in tumorigenesis and cell transformation, has been reported to naturally occur in a variety of human cancers [4][5][6][7][8][9][10][11][12], with elevated expression of AURKA also correlated with poor prognosis and higher grade of tumor [13]. Due to frequent involvement and compelling evidence in favor of AURKA and AURKB being associated with cancer etiopathology, the molecular mechanisms underlying their genetic and biochemical regulation as well as molecular interactions in various cancer relevant pathways have been investigated.…”