Enhanced expression of proproliferative and antiapoptotic genes in ulcerative colitis-associated neoplasia
Article first published online: 21 DEC 2009
Copyright © 2009 Crohn's & Colitis Foundation of America, Inc.
Inflammatory Bowel Diseases
Volume 16, Issue 7, pages 1127–1137, July 2010
How to Cite
Švec, J., Musílková, J., Bryndová, J., Jirásek, T., Mandys, V., Kment, M. and Pácha, J. (2010), Enhanced expression of proproliferative and antiapoptotic genes in ulcerative colitis-associated neoplasia. Inflamm Bowel Dis, 16: 1127–1137. doi: 10.1002/ibd.21178
- Issue published online: 11 JUN 2010
- Article first published online: 21 DEC 2009
- Manuscript Accepted: 22 OCT 2009
- Manuscript Received: 30 SEP 2009
- Ministry of Health. Grant Numbers: IGA 1A/8651-4, NS 9982-4)
- Ministry of Education, Youth and Sports (Project Oncology). Grant Number: MSM 002120808
- Academy of Sciences. Grant Numbers: IAA500110605, AV0Z 50110509
- ulcerative colitis;
- colorectal cancer;
- proproliferative and antiapoptotic markers
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.
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.
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.
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. (Inflamm Bowel Dis 2010)