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Exp Mol Med. 2010 Nov 30;42(11):759-67.

Suppression of Aurora-A oncogenic potential by c-Myc downregulation.

Author information

1
State Key Laboratory of Molecular Oncology and Laboratory of Cell and Molecular Biology, Cancer Institute and Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Abstract

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.

PMID:
20890087
PMCID:
PMC2992855
DOI:
10.3858/emm.2010.42.11.077
[Indexed for MEDLINE]
Free PMC Article

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