This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yang, H. Articles by Cheng, J. Q. Search for Related Content PubMed PubMed Citation Articles by Yang, H. Articles by Cheng, J. Q.

Aurora-A Kinase Regulates Telomerase Activity through c-Myc in Human Ovarian and Breast Epithelial Cells

¹ Department of Pathology and Molecular Oncology Program, University of South Florida College of Medicine and H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, and
² Cancer Research Department, Berlex Biosciences, Richmond, California

Aurora-A kinase is frequently overexpressed/activated in human ovarian and breast cancers. A rat mammary tumor model study indicates that alterations of Aurora-A are early events during mammary tumor development (T. M. Goepfert et al., Cancer Res., 62: 4115–4122, 2002), suggesting that Aurora-A plays a pivotal role in transformation. However, the molecular mechanism by which Aurora-A induces ovarian and breast cell transformation remains elusive. Here we show that ectopic expression of Aurora-A induces telomerase activity in human ovarian and breast epithelial cell lines HIOSE118 and MCF-10A. The mRNA and promoter activities of human telomerase reverse transcriptase (hTERT) are stimulated by Aurora-A. Furthermore, we have demonstrated that the c-Myc binding sites of hTERT promoter are required for Aurora-A-induced hTERT promoter activity. Ectopic expression of Aurora-A up-regulates c-Myc. Knockdown of c-Myc by RNA interference attenuates Aurora-A-stimulated hTERT expression and telomerase activity. To our knowledge, these findings demonstrate, for the first time, that Aurora-A induces telomerase activity and hTERT by up-regulation of c-Myc and provides an additional mechanism for the role of Aurora-A in malignant transformation in addition to its cell cycle control.

This article has been cited by other articles:

				H. Yang, W. Kong, L. He, J.-J. Zhao, J. D. O'Donnell, J. Wang, R. M. Wenham, D. Coppola, P. A. Kruk, S. V. Nicosia, et al. MicroRNA Expression Profiling in Human Ovarian Cancer: miR-214 Induces Cell Survival and Cisplatin Resistance by Targeting PTEN Cancer Res., January 15, 2008; 68(2): 425 - 433. [Abstract] [Full Text] [PDF]

				E Burum-Auensen, P M DeAngelis, A R Schjolberg, J. Roislien, S N Andersen, and O P F Clausen Spindle proteins Aurora A and BUB1B, but not Mad2, are aberrantly expressed in dysplastic mucosa of patients with longstanding ulcerative colitis J. Clin. Pathol., December 1, 2007; 60(12): 1403 - 1408. [Abstract] [Full Text] [PDF]

				C. N. Landen Jr., Y. G. Lin, A. Immaneni, M. T. Deavers, W. M. Merritt, W. A. Spannuth, D. C. Bodurka, D. M. Gershenson, W. R. Brinkley, and A. K. Sood Overexpression of the Centrosomal Protein Aurora-A Kinase is Associated with Poor Prognosis in Epithelial Ovarian Cancer Patients Clin. Cancer Res., July 15, 2007; 13(14): 4098 - 4104. [Abstract] [Full Text] [PDF]

				J. Fu, M. Bian, Q. Jiang, and C. Zhang Roles of Aurora Kinases in Mitosis and Tumorigenesis Mol. Cancer Res., January 1, 2007; 5(1): 1 - 10. [Abstract] [Full Text] [PDF]

				J.-C. Wu, T.-Y. Chen, C.-T. R. Yu, S.-J. Tsai, J.-M. Hsu, M.-J. Tang, C.-K. Chou, W.-J. Lin, C.-J. Yuan, and C.-Y. F. Huang Identification of V23RalA-Ser194 as a Critical Mediator for Aurora-A-induced Cellular Motility and Transformation by Small Pool Expression Screening J. Biol. Chem., March 11, 2005; 280(10): 9013 - 9022. [Abstract] [Full Text] [PDF]

				T. Tong, Y. Zhong, J. Kong, L. Dong, Y. Song, M. Fu, Z. Liu, M. Wang, L. Guo, S. Lu, et al. Overexpression of Aurora-A Contributes to Malignant Development of Human Esophageal Squamous Cell Carcinoma Clin. Cancer Res., November 1, 2004; 10(21): 7304 - 7310. [Abstract] [Full Text] [PDF]