| Mechanism of telomerase repression during terminal differentiation of normal epithelial cells and squamous carcinoma lines. | |
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MedLine Citation:
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PMID: 16077937 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Stratified squamous epithelial cells undergo an orderly process of cell cycle arrest following detachment from the basement membrane. The basal layer cells which adhere to the basement membrane express telomerase, which maintains the ends of chromosomes in this rapidly dividing population. Non-dividing suprabasal cells downregulate telomerase activity. However, the mechanisms regulating this inhibition are unknown. We examined the regulation of telomerase expression in anchorage-deprived normal human epidermal keratinocytes and squamous cell carcinoma lines. Anchorage-deprived cells underwent rapid loss of telomerase activity. Attachment loss was associated with increased ERK1 activity, G1 to S phase progression, and subsequent G2 arrest. Adhesion to collagen via specific integrin subunits inhibited ERK1 activity and telomerase repression. Loss of telomerase expression was associated with recruitment of an Rb/HDAC1 repressor complex to the -98 E2F site of the hTERT promoter. We propose a mechanism by which anchorage deprivation inhibits telomerase activity in stratified squamous epithelial cells and squamous cell carcinoma lines. |
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Authors:
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David L Crowe; Dan C Nguyen; Arthur Ohannessian |
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Publication Detail:
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Type: Comparative Study; Journal Article |
Journal Detail:
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Title: International journal of oncology Volume: 27 ISSN: 1019-6439 ISO Abbreviation: Int. J. Oncol. Publication Date: 2005 Sep |
Date Detail:
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Created Date: 2005-08-03 Completed Date: 2005-09-12 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 9306042 Medline TA: Int J Oncol Country: Greece |
Other Details:
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Languages: eng Pagination: 847-54 Citation Subset: IM |
Affiliation:
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Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, CA 90033, USA. dcrowe@usc.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Binding Sites Blotting, Western Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors Carcinoma, Squamous Cell / enzymology*, pathology Cell Cycle Cell Differentiation* Cell Line, Tumor Cells, Cultured Collagen Type IV / pharmacology Cyclin A / analysis Cyclin B / analysis DNA-Binding Proteins / genetics, metabolism Enzyme Activation / drug effects Epithelial Cells / cytology, drug effects, metabolism* Flavonoids / pharmacology Flow Cytometry Gene Expression Regulation, Enzymologic / drug effects Histone Deacetylase 1 Histone Deacetylases / genetics, metabolism Humans Keratinocytes / cytology, drug effects, metabolism Mitogen-Activated Protein Kinase 3 / metabolism Phosphorylation / drug effects Promoter Regions, Genetic / genetics Protein Binding RNA, Messenger / genetics, metabolism Retinoblastoma Protein / genetics, metabolism Reverse Transcriptase Polymerase Chain Reaction Telomerase / genetics, metabolism* |
| Chemical | |
Reg. No./Substance:
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0/Collagen Type IV; 0/Cyclin A; 0/Cyclin B; 0/DNA-Binding Proteins; 0/Flavonoids; 0/PD 98059; 0/RNA, Messenger; 0/Retinoblastoma Protein; EC 2.7.11.17/Calcium-Calmodulin-Dependent Protein Kinases; EC 2.7.11.24/Mitogen-Activated Protein Kinase 3; EC 2.7.7.49/Telomerase; EC 3.5.1.98/HDAC1 protein, human; EC 3.5.1.98/Histone Deacetylase 1; EC 3.5.1.98/Histone Deacetylases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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