NDLI: Transcriptome signature of irreversible senescence in human papillomavirus-positive cervical cancer cells.

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Transcriptome signature of irreversible senescence in human papillomavirus-positive cervical cancer cells.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Aronow, Bruce J. Wise, Trisha M. Couget, Jennifer A. Williams, Sarah S. Wells, Susanne I. Howley, Peter M.
Description	Author Affiliation: Wells SI ( Department of Pathology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA.);
Abstract	A frequent characteristic of human papillomavirus (HPV)-positive cervical cancers is the loss of viral E2 gene expression in HPV-infected cervical epithelial cells as a consequence of viral DNA integration into the cellular genome. The expression of E2 in HPV-positive cancer cells results in the repression of the viral E6/E7 oncogenes, activation of the p53 and pRB pathways, and a G1 cell cycle arrest, followed by induction of cellular senescence. The transcriptional consequences of E2-mediated cell cycle arrest that lead to senescence currently are unknown. Using conditional senescence induction in HeLa cells and microarray analysis, we describe here the expression profile of cells irreversibly committed to senescence. Our results provide insight into the molecular anatomy of senescence pathways and its regulation by HPV on-coproteins. These include the induction of the RAB vesicular transport machinery and a general down-regulation of chromatin regulatory molecules. The repression of tumor-specific G antigens during E2 senescence supports a reversal of the tumorigenic phenotype by E2 and the potential approach of tumor-specific G antigen-specific immunotherapy for cervical cancer.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	12
Volume Number	100
Language	English
Publisher	National Academy of Sciences
Publisher Date	2003-06-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Papillomaviridae Genetics Pathogenicity Papillomavirus Infections Virology Tumor Virus Infections Uterine Cervical Neoplasms Adenoviridae Bovine Papillomavirus 1 Cell Aging Cyclin-Dependent Kinase Inhibitor P21 Cyclins DNA, Neoplasm DNA, Viral Gene Expression Gene Expression Profiling Genetic Vectors HeLa Cells Mutation Oligonucleotide Array Sequence Analysis Oncogene Proteins, Viral Pathology Therapy Phenotype RNA, Messenger Metabolism RNA, Neoplasm Temperature Transcription, Genetic Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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