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KMID : 0620920100420110759
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Experimental & Molecular Medicine
2010 Volume.42 No. 11 p.759 ~ p.767
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Suppression of Aurora-A oncogenic potential by c-Myc downregulation
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Yang Shangbin
He Shun
Zhou Xiaobo
Liu Mei
Zhu Hongxia
Wang Yihua
Zhang Wei
Quan Lanping
Bai Jingfeng
Xu Ningzhi
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Abstract
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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.
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KEYWORD
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aurora kinase, neoplasms, proto-oncogene proteins c-myc, RNA interference
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