Herbst, Andreas and Bommer, Guido T. and Kriegl, Lydia and Jung, Andreas and Behrens, Andrea and Csanadi, Endy and Gerhard, Markus and Bolz, Christian and Riesenberg, Rainer and Zimmermann, Wolfgang and Dietmaier, Wolfgang and Wolf, Isabella and Brabletz, Thomas and Goeke, Burkhard and Kolligs, Frank T. (2009) ITF-2 Is Disrupted via Allelic Loss of Chromosome 18q21, and ITF-2B Expression Is Lost at the Adenoma-Carcinoma Transition. GASTROENTEROLOGY, 137 (2). pp. 639-648. ISSN 0016-5085, 1528-0012
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BACKGROUND & AIMS: The ubiquitously expressed basic helix-loop-helix transcription factor ITF-2B has an important role in differentiation processes, and its transcription is regulated by beta-catenin. The ITF-2 gene is located in the chromosomal region 1.8q21; allelic loss of this locus Occurs in 70% of colorectal cancers. We analyzed the expression, regulation, and function of ITF-2B in colorectal carcinogenesis. METHODS: The loss-of-heterozygosity (LOH) status of 18q21 and expression of ITF-2B were Studied in colorectal carcinomas using polymerase chain reaction-based methods and immunohistochemistry. The biologic effects of ITF-2B were studied in colorectal cancer cells. Reporter gene assays and chromatin immunoprecipitation were utilized to analyze effects of ITF-2B on gene transcription. RESULTS: ITF-2B is strongly expressed in colon adenomas but frequently down-regulated in carcinomas because of LOH at 18q21. ITF-2B induces cell cycle arrest and regulates the expression of p21(Cip1) via newly identified E-boxes in the CDKN1A gene, independently of p53. Loss of ITF-2B expression correlates with loss of p21(Cip1) expression in primary colon carcinomas. CONCLUSIONS: Accumulation of mutations and allelic losses are driving forces of colorectal carcinogenesis. ITF-2B, which is up-regulated during early colorectal carcinogenesis because of loss of adenomatous polyposis coli, is a target for LOH on chromosome 18q, along with deleted in colorectal carcinoma and Smad4. This finding, along with the fact that ITF-2B is a regulator of the key cell cycle inhibitor p21(Cip1), indicates that ITF-2B is a tumor suppressor that has an important function at the adenoma to carcinoma transition.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | II COLORECTAL-CANCER; LOOP-HELIX PROTEINS; CELL-CYCLE; BETA-CATENIN; P53; TRANSFORMATION; PROGRESSION; PROGNOSIS; ARREST; GENE; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 10 Sep 2020 12:32 |
| Last Modified: | 10 Sep 2020 12:32 |
| URI: | https://pred.uni-regensburg.de/id/eprint/28623 |
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