| Association of hsp90 to the hTERT promoter is necessary for hTERT expression in human oral cancer cells. | |
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MedLine Citation:
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PMID: 18820283 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Enhanced expression of human telomerase reverse transcriptase (hTERT) occurs frequently during cellular immortalization. The current study was undertaken to determine the mechanism regulating the hTERT promoter activity during cellular immortalization of human oral keratinocytes. Normal human oral keratinocytes (NHOKs) were immortalized with Bmi-1 and the E6 oncoprotein of human papillomavirus type 16 to establish the telomerase-positive HOK-Bmi-1/E6 cell line. Using DNA-protein-binding assay, we found that heat shock protein 90 (hsp90) physically interacts with the hTERT promoter in vitro. The hsp90 interaction with the promoter was detected more strongly in the telomerase-positive HOK-Bmi-1/E6 cells compared with that in senescing NHOK. Chromatin immunoprecipitation confirmed the in vivo interaction between hsp90 and the hTERT promoter in SCC4 cells, a telomerase-positive oral cancer cell line, but not in the NHOK. To determine the physiological significance of this interaction, SCC4 cells were exposed to geldanamycin (GA), a competitive inhibitor of hsp90. GA exposure led to decrease in telomerase activity, hTERT promoter activity and hTERT messenger RNA expression in SCC4 cells, even in the absence of de novo protein synthesis. Also, it abolished the in vivo interaction of the hTERT promoter region with hsp90 but not with Sp1 or c-Myc. These results indicate that physical interaction between hsp90 and the hTERT promoter occurs in telomerase-positive cells but not in normal human cells and is necessary for the enhanced hTERT expression and telomerase activity in cancer cells. |
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Authors:
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Reuben H Kim; Roy Kim; Wei Chen; Shen Hu; Ki-Hyuk Shin; No-Hee Park; Mo K Kang |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2008-09-26 |
Journal Detail:
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Title: Carcinogenesis Volume: 29 ISSN: 1460-2180 ISO Abbreviation: Carcinogenesis Publication Date: 2008 Dec |
Date Detail:
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Created Date: 2008-12-03 Completed Date: 2009-01-28 Revised Date: 2012-03-13 |
Medline Journal Info:
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Nlm Unique ID: 8008055 Medline TA: Carcinogenesis Country: England |
Other Details:
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Languages: eng Pagination: 2425-31 Citation Subset: IM |
Affiliation:
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University of California, Los Angeles School of Dentistry, Center for the Health Sciences, Los Angeles, CA 90095, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Blotting, Western Cell Line, Transformed Cell Line, Tumor Cell Transformation, Neoplastic / genetics* Chromatography, Liquid Gene Expression / physiology* HSP90 Heat-Shock Proteins / metabolism* Humans Immunoprecipitation Keratinocytes / metabolism Mouth Neoplasms / genetics*, metabolism Promoter Regions, Genetic RNA, Messenger / analysis Reverse Transcriptase Polymerase Chain Reaction Tandem Mass Spectrometry Telomerase / genetics*, metabolism |
| Grant Support | |
ID/Acronym/Agency:
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K02 DE018959-01/DE/NIDCR NIH HHS; K02 DE018959-05/DE/NIDCR NIH HHS; K02 DE18959/DE/NIDCR NIH HHS; K08 DE017121-05/DE/NIDCR NIH HHS; K08 DE17121/DE/NIDCR NIH HHS; R01 DE018295-02/DE/NIDCR NIH HHS; R01 DE14147/DE/NIDCR NIH HHS; R01 DE18295/DE/NIDCR NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/HSP90 Heat-Shock Proteins; 0/RNA, Messenger; EC 2.7.7.49/Telomerase |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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