Abstract
Background.
Aurora kinase A (AURKA) is amplified with varying incidence in multiple human cancers including head and neck squamous cell carcinoma (HNSCC). We investigated whether AURKA is a potential therapeutic target in HNSCC.
Methods.
We conducted an immunohistochemical analysis of AURKA expression in paired normal and tumor samples (n = 63). HNSCC cells treated with siRNA specific for AURKA were assessed for AURKA mRNA and protein expression levels by reverse transcriptaseโpolymerase chain reaction and Western blot analysis. Tumor cells treated with siRNA and paclitaxel were assessed for cell proliferation by MTT assay and for cell cycle distribution by flow cytometry.
Results.
AURKA expression was higher in tumor than in adjacent normal in most (85%) of the samples analyzed. HNSCC cells and primary tumors revealed high expression levels of AURKA. Most primary tumors also showed high kinase activity of the enzyme. Targeted AURKA inhibition increased the subโG1 cell fraction, with a concomitant reduction in the G1 cell population, indicating induction of apoptosis and thus markedly suppressed proliferation of HNSCC cells. Combining siRNAโinduced AURKA inhibition with 5 to 10 n__M__ paclitaxel synergistically enhanced apoptosis induction.
Conclusion.
AURKA is a potential therapeutic target for HNSCC. Further investigation of smallโmolecule AURKA inhibitors as therapeutic agents is warranted. ยฉ 2008 Wiley Periodicals, Inc. Head Neck, 2009