gms | German Medical Science

27. Deutscher Krebskongress

Deutsche Krebsgesellschaft e. V.

22. - 26.03.2006, Berlin

ITF-2 is a candidate tumor suppressor gene located on chromosome 18q21

Meeting Abstract

  • corresponding author presenting/speaker Andreas Herbst - Uniklinikum Großhadern, München, Deutschland
  • Guido Bommer - Uniklinikum Großhadern, München
  • Andrea Behrens - Uniklinikum Großhadern, München
  • Claudia Jäger - Uniklinikum Großhadern, München
  • Thomas Brabletz - Inst. für Pathologie, Universität Erlangen
  • Burkhard Göke - Uniklinikum Großhadern, München
  • Frank T. Kolligs - Uniklinikum Großhadern, München

27. Deutscher Krebskongress. Berlin, 22.-26.03.2006. Düsseldorf, Köln: German Medical Science; 2006. DocOP487

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Veröffentlicht: 20. März 2006

© 2006 Herbst et al.
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Background: Colorectal cancer is characterized by a number of specific genetic changes. Among these, inactivation of the tumor suppressor genes APC (adenomatous polyposis coli) and p53 are the most prominent ones. The majority of colon carcinomas also displays loss of heterozygosity (LOH) on chromosome 18q21. This chromosomal region contains the genes for DCC (deleted in colon carcinoma) and DPC / Smad4 (deleted in pancreatic cancer) as well as the gene for the basic helix-loop-helix transcription factor ITF-2 (immunoglobulin transcription factor 2).

Aim of study: To analyse mRNA-expression of ITF-2 in primary colorectal cancers and matched normal colon epithelium. To characterize the function of ITF-2 and evaluate its importance for the development of colon cancer.

Results: The expression of ITF-2B is significantly down-regulated or lost in the majority of primary colorectal cancers as well as colorectal cancer cell lines. Using a tetracycline-inducible expression system for ITF-2 (isoform B), we were able to show that re-expression of ITF-2B inhibits proliferation of DLD-1 and SW480 colon carcinoma cell lines. Closer analysis revealed that attenuated proliferation is caused by an arrest of the cell cycle in the G1 phase. In contrast, no effect on apoptosis was detected. Using a DNA microarray approach to identify ITF-2B target genes that might be responsible for the cell cycle arrest, we discovered that the cell cycle inhibitor p21(Cip1) is regulated in an ITF-2B dependent manner. Further experiments confirmed that ITF- 2B expression correlates with an increase in p21(Cip1) expression and induction of cell cycle arrest.

Conclusions: LOH on 18q21 affects the gene encoding the transcription factor ITF-2. Analysis of colorectal carcinomas revealed that ITF-2B expression is lost in approximately 70% of cases. Re-expression of ITF-2B in colorectal cancer cell lines with little or no endogenous ITF-2B expression revealed that ITF-2B is capable of inhibiting cellular growth by arresting cell cycle progression. We therefore conclude, that the gene encoding ITF-2B has a tumor suppressive function in colorectal cancer. Loss of ITF-2B expression provides a growth advantage for the affected colon cancer cell.