Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2004-1-27
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
64
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
463-7
pubmed:dateRevised
2011-7-11
pubmed:meshHeading
pubmed-meshheading:14744757-Breast, pubmed-meshheading:14744757-Cell Cycle Proteins, pubmed-meshheading:14744757-Cell Line, pubmed-meshheading:14744757-DNA Primers, pubmed-meshheading:14744757-DNA-Binding Proteins, pubmed-meshheading:14744757-Epithelial Cells, pubmed-meshheading:14744757-Female, pubmed-meshheading:14744757-Gene Expression Regulation, pubmed-meshheading:14744757-Humans, pubmed-meshheading:14744757-Kinetics, pubmed-meshheading:14744757-Ovary, pubmed-meshheading:14744757-Promoter Regions, Genetic, pubmed-meshheading:14744757-Protein Kinases, pubmed-meshheading:14744757-Protein-Serine-Threonine Kinases, pubmed-meshheading:14744757-Proto-Oncogene Proteins c-myc, pubmed-meshheading:14744757-RNA, Messenger, pubmed-meshheading:14744757-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:14744757-Telomerase, pubmed-meshheading:14744757-Transcription, Genetic, pubmed-meshheading:14744757-Xenopus Proteins
pubmed:year
2004
pubmed:articleTitle
Aurora-A kinase regulates telomerase activity through c-Myc in human ovarian and breast epithelial cells.
pubmed: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.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S.