Aurora-A kinase regulates telomerase activity through c-Myc in human ovarian and breast epithelial cells.
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.
Yang
Hua
H
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.
Ou
Chien Chen
CC
Feldman
Richard I
RI
Nicosia
Santo V
SV
Kruk
Patricia A
PA
Cheng
Jin Q
JQ
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
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