Document Detail


Changes in telomerase activity, expression and splicing in response to differentiation of normal and carcinoma colon cells.
MedLine Citation:
PMID:  12820429     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Jirí Fajkus; Marek Borsky; Zuzana Kunická; Martiná Kovaríková; Dana Dvoráková; Jirina Hofmanová; Alois Kozubík
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Anticancer research     Volume:  23     ISSN:  0250-7005     ISO Abbreviation:  Anticancer Res.     Publication Date:    2003 Mar-Apr
Date Detail:
Created Date:  2003-06-24     Completed Date:  2003-07-25     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8102988     Medline TA:  Anticancer Res     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  1605-12     Citation Subset:  IM    
Affiliation:
Institute of Biophysics, Academy of Sciences of the Czech Republic, Královopolská 135, CZ-61265 Brno, Czech Republic. fajkus@ibp.cz
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MeSH Terms
Descriptor/Qualifier:
Adenocarcinoma / 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:
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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