Document Detail


Enhanced expression of proproliferative and antiapoptotic genes in ulcerative colitis-associated neoplasia.
MedLine Citation:
PMID:  20027603     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Inflammatory bowel diseases including long-standing ulcerative colitis (UC) have an increased risk of evolving into colorectal cancer (CRC). The overexpression of some proproliferative and antiapoptotic genes, such as survivin, telomerase catalytic subunit (hTERT), integrin-linked kinase (ILK), and regulatory factors c-MYB and Tcf-4, has been implicated in the development and progression of several human malignancies including CRC.
METHODS: In this study we analyzed the expression alterations of these markers and proinflammatory enzymes cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS) during the transition of colonic mucosa from chronic inflammation to epithelial neoplasia in biopsies of UC patients using quantitative real-time polymerase chain reaction and immunohistochemistry; additionally, we compared the expression profiles of this gene panel in samples of patients with CRC after tumor resection and in human tumor xenografts of SW620 malignant colonic cells.
RESULTS: The transcript levels of survivin, c-MYB, COX-2, iNOS, and Tcf-4 showed a statistically significant increase during neoplastic transformation of UC patient colonic mucosa, whereas hTERT and ILK were not elevated. In contrast, the specimens of CRC showed upregulated expression of not only survivin, c-MYB, Tcf-4, COX-2, and iNOS but also hTERT. A similar expression profile was observed in human tumor xenografts in which all transcripts with the exception of c-MYB were upregulated.
CONCLUSIONS: These results suggest that telomerase and ILK activation occurs during the later stages of carcinoma progression, whereas upregulation of survivin, c-MYB, and Tcf-4 is a feature of the early stage of development of neoplasia, and thus, they might serve as early indicators for UC-associated colorectal carcinogenesis.
Authors:
Jirí Svec; Jana Musílková; Jana Bryndová; Tomás Jirásek; Václav Mandys; Milan Kment; Jirí Pácha
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Inflammatory bowel diseases     Volume:  16     ISSN:  1536-4844     ISO Abbreviation:  Inflamm. Bowel Dis.     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-06-21     Completed Date:  2010-09-30     Revised Date:  2011-10-27    
Medline Journal Info:
Nlm Unique ID:  9508162     Medline TA:  Inflamm Bowel Dis     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1127-37     Citation Subset:  IM    
Affiliation:
Second Department of Internal Medicine, Third Faculty of Medicine, Charles University, Prague, Czech Republic.
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Aged, 80 and over
Animals
Apoptosis
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / genetics*,  metabolism
Blotting, Western
Cell Proliferation
Colitis, Ulcerative / complications,  genetics*,  metabolism
Colorectal Neoplasms / etiology,  metabolism*,  pathology
Cyclooxygenase 2 / genetics*,  metabolism
Female
Genes, myb / genetics*
Humans
Immunoenzyme Techniques
Male
Mice
Mice, Nude
Microtubule-Associated Proteins / genetics*,  metabolism
Middle Aged
Nitric Oxide Synthase Type II / genetics*,  metabolism
Prognosis
RNA, Messenger / genetics
Reverse Transcriptase Polymerase Chain Reaction
Telomerase / genetics*,  metabolism
Transcription Factors / genetics*,  metabolism
Chemical
Reg. No./Substance:
0/BIRC5 protein, human; 0/Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; 0/Microtubule-Associated Proteins; 0/RNA, Messenger; 0/TCF4 protein, human; 0/Transcription Factors; EC 1.14.13.39/NOS2 protein, human; EC 1.14.13.39/Nitric Oxide Synthase Type II; EC 1.14.99.1/Cyclooxygenase 2; EC 1.14.99.1/PTGS2 protein, human; EC 2.7.7.49/TERT protein, human; EC 2.7.7.49/Telomerase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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