| Changes in telomerase activity, expression and splicing in response to differentiation of normal and carcinoma colon cells. | |
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MedLine Citation:
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PMID: 12820429 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Telomerase, a ribonucleoprotein complex catalysing synthesis of telomeric DNA, is an essential cellular immortalizing factor whose activation is a critical step in the progression to malignancy. An important agent maintaining the balance between proliferation, differentiation and apoptosis of intestinal epithelial cells in crypts is butyrate, which is formed in the gastrointestinal tract by anaerobic bacterial fermentation. It inhibits cell growth, induces differentiation and triggers apoptosis in neoplastic colonocytes. MATERIALS AND METHODS: In this study, the responses of adenocarcinoma (HT-29) and fetal (FHC) human colon cells to 5 mM sodium butyrate (NaBt) have been compared. RESULTS: Despite the similar general response of both cell lines to NaBt, i.e., G0/G1 arrest, decrease of growth rate and increase of differentiation (as indicated by alkaline phosphatase activity), they differ in the level and dynamics of the measured parameters. Telomerase activity and the level of mRNA for its catalytic subunit (hTERT) decline significantly after 48 hours, reaching a complete inhibition after 144 hours. While both cell lines show similar kinetics of hTERT transcriptional silencing, the down-regulation of telomerase activity is faster in FHC cells. Correspondingly, we show that a candidate posttranscriptional regulation step, differential splicing of hTERT mRNA, may be involved in the faster loss of telomerase activity in FHC cells. CONCLUSION: Differences in hTERT mRNA splicing may represent a useful marker of telomere metabolism in normal and malignant colon cells and that these changes may be connected with different cytokinetic patterns of these cells. |
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Authors:
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Jirí Fajkus; Marek Borsky; Zuzana Kunická; Martiná Kovaríková; Dana Dvoráková; Jirina Hofmanová; Alois Kozubík |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Anticancer research Volume: 23 ISSN: 0250-7005 ISO Abbreviation: Anticancer Res. Publication Date: 2003 Mar-Apr |
Date Detail:
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Created Date: 2003-06-24 Completed Date: 2003-07-25 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 8102988 Medline TA: Anticancer Res Country: Greece |
Other Details:
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Languages: eng Pagination: 1605-12 Citation Subset: IM |
Affiliation:
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Institute of Biophysics, Academy of Sciences of the Czech Republic, Královopolská 135, CZ-61265 Brno, Czech Republic. fajkus@ibp.cz |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adenocarcinoma
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genetics,
metabolism* Apoptosis / drug effects Butyrates / pharmacology Cell Cycle / drug effects Cell Differentiation / drug effects Cell Division / drug effects Cells, Cultured / cytology, drug effects, metabolism Colon / embryology, metabolism* Colonic Neoplasms / pathology* DNA-Binding Proteins Enzyme Induction / drug effects Gene Expression Regulation, Neoplastic* / drug effects Humans Neoplasm Proteins / genetics, metabolism* RNA Splicing* RNA, Messenger / metabolism RNA, Neoplasm / metabolism Telomerase / genetics, metabolism* Telomere / metabolism Tumor Cells, Cultured / cytology, drug effects, metabolism |
| Chemical | |
Reg. No./Substance:
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0/Butyrates; 0/DNA-Binding Proteins; 0/Neoplasm Proteins; 0/RNA, Messenger; 0/RNA, Neoplasm; EC 2.7.7.49/Telomerase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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