title: Inactivation of Itf2 promotes intestinal tumorigenesis in Apc(Min/+) mice.
abstract: Deregulation of Wnt/β-catenin signaling following inactivation of the adenomatous polyposis coli (APC) tumor suppressor gene is frequently found in colorectal cancer. We have previously shown that levels of ITF-2B, encoded by the β-catenin target gene ITF2 that is located on the tumor suppressor gene locus 18q21, are increased in colonic adenomas with deregulated β-catenin activity. However, during tumor progression ITF-2B levels are reduced, suggesting that ITF-2B interferes with tumor development. To investigate the role of ITF2 in intestinal tumorigenesis, we specifically inactivated Itf2 in the intestinal epithelium of Apc(Min/+) mice. We found that genetic disruption of Itf2 on the Apc(Min/+) background results in earlier death and a significant increase in tumor number and size in the small intestine. Based on these data Itf2 acts as a tumor suppressor gene of the intestinal tract that inhibits tumor initiation and growth.
authors: Department of Medicine II, University of Munich, 81377 Munich, Germany; Institute of Molecular Animal Breeding and Biotechnology, Gene Center, University of Munich, 81377 Munich, Germany. Electronic address: grill@genzentrum.lmu.de.
authors: Jessica I
authors: JI
authors: Grill
authors: Department of Medicine II, University of Munich, 81377 Munich, Germany.
authors: Andreas
authors: A
authors: Herbst
authors: Institute of Pathology, University of Munich, 80337 Munich, Germany.
authors: Lydia
authors: L
authors: Brandl
authors: Department of Medicine II, University of Munich, 81377 Munich, Germany.
authors: Lixia
authors: L
authors: Kong
authors: Institute of Molecular Animal Breeding and Biotechnology, Gene Center, University of Munich, 81377 Munich, Germany.
authors: Marlon R
authors: MR
authors: Schneider
authors: Institute of Pathology, University of Munich, 80337 Munich, Germany.
authors: Thomas
authors: T
authors: Kirchner
authors: Institute of Molecular Animal Breeding and Biotechnology, Gene Center, University of Munich, 81377 Munich, Germany.
authors: Eckhard
authors: E
authors: Wolf
authors: Department of Medicine II, University of Munich, 81377 Munich, Germany; German Cancer Consortium (DKTK), 69120 Heidelberg, Germany; German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; Department of Internal Medicine and Gastroenterology, HELIOS Klinikum Berlin-Buch, Berlin, Germany.
authors: Frank T
authors: FT
authors: Kolligs
mesh_terms: D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics*; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D017491:Genes, APC; D007414:Intestinal Neoplasms / Q000235:genetics* / Q000473:pathology*; D007421:Intestine, Small / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D000073940:Transcription Factor 4
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; C090743:Tcf4 protein, mouse; D000073940:Transcription Factor 4
keywords: Apc(Min/+) mouse; ITF2; Intestinal cancer