Overexpression of Aurora-A kinase promotes tumor cell proliferation and inhibits apoptosis in esophageal squamous cell carcinoma cell line

Aurora-A kinase,a serine/threonine protein kinase,is a potential oncogene.Amplification and overexpression of Au- rora-A have been found in several types of human tumors,including esophageal squamous cell carcinoma(ESCC).It has been demonstrated that cells overexpressing Aurora-A are more resistant to cisplatin-induced apoptosis.However,the molecular mechanisms mediating these effects remain largely unknown.In this report,we showed that overexpression of Aurora-A through stable transfection of pEGFP-Aurora-A in human ESCC KYSE150 cells significantly promoted cell proliferation and inhibited cisplatin- or UV irradiation-induced apoptosis.Cleavages of caspase-3 and poly(ADP- ribose)polymerase(PARP)in Aurora-A overexpressing cells were substantially reduced after cisplatin or UV treatment. Furthermore,we found that silencing of endogenous Aurora-A kinase with siRNA substantially enhanced sensitivity to cisplatin- or UV-induced apoptosis in human ESCC EC9706 cells.In parallel,overexpression of Aurora-A potently upregulated the expression of Bc1-2.Moreover,the knockdown of Bc1-2 by siRNA abrogated the Aurora-A's effect on inhibiting apoptosis.Taken together,these data provide evidence that Aurora-A overexpression promoting cell proliferation and inhibiting apoptosis,suggesting a novel mechanism that is closely related to malignant phenotype and anti-cancer drugs resistance of ESCC cells.