The abnormality of serine/threonine kinase Aurora-A is seen in many types of cancers. Although in physiological context it has been shown to play a vital role in cellular mitosis, how this oncogene contributes to tumorigenesis remains unclear. Here we demonstrate that Aurora-A overexpression enhances both the expression level and transcriptional activity of c-Myc. The inhibition of c-Myc expression by RNA interference significantly impaired the oncogenic potential of Aurora-A, resulting in attenuated cellular proliferation and transformation rates as well as fewer centrosomal aberrations. Furthermore, downregulation of c-Myc effectively overcame Aurora-A-induced resistance to cisplatin in esophageal cancer cells. Taken together, our results suggest an important role for c-Myc in mediating the oncogenic activity of Aurora-A, which may in turn allow for future targeting of c-Myc as a potential therapeutic strategy for tumors with Aurora-A overexpression.
Cell Line, Transformed ; Cell Proliferation/drug effects ; Cell Transformation, Neoplastic/drug effects/genetics ; Centro ; Chromo ; Cisplatin/pharmacology ; Down-Regulation ; E ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Protein-Serine-Threonine Kinases/genetics/*metabolism ; Proto-Oncogene Proteins c-myc/genetics/*metabolism ; RNA, Small Interfering/genetics ; Transcriptional Activation ; Transgenes/genetics