title: Aurora-A kinase regulates telomerase activity through c-Myc in human ovarian and breast epithelial cells.
abstract: 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.
authors.affiliation: 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, USA.
authors.forename: Hua
authors.initials: H
authors.lastname: Yang
authors.forename: Chien Chen
authors.initials: CC
authors.lastname: Ou
authors.forename: Richard I
authors.initials: RI
authors.lastname: Feldman
authors.forename: Santo V
authors.initials: SV
authors.lastname: Nicosia
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Kruk
authors.forename: Jin Q
authors.initials: JQ
authors.lastname: Cheng
mesh_terms: D064096:Aurora Kinase A; D064127:Aurora Kinases; D001940:Breast / Q000166:cytology / Q000201:enzymology / Q000502:physiology; D018797:Cell Cycle Proteins; D002460:Cell Line; D017931:DNA Primers; D004268:DNA-Binding Proteins; D004847:Epithelial Cells / Q000201:enzymology / Q000502:physiology; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007700:Kinetics; D010053:Ovary / Q000201:enzymology / Q000502:physiology*; D011401:Promoter Regions, Genetic; D011494:Protein Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019098:Telomerase / Q000235:genetics* / Q000378:metabolism*; D014158:Transcription, Genetic; D029867:Xenopus Proteins
chemical_list: D018797:Cell Cycle Proteins; D017931:DNA Primers; D004268:DNA-Binding Proteins; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D029867:Xenopus Proteins; D011494:Protein Kinases; C112134:AURKA protein, Xenopus; C576920:Aurka protein, rat; D064096:Aurora Kinase A; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; D019098:Telomerase