Itf2的失活促进Apc(Min/+)小鼠的肠道肿瘤发生。

Inactivation of Itf2 promotes intestinal tumorigenesis in Apc(Min/+) mice.

作者信息

Grill Jessica I, Herbst Andreas, Brandl Lydia, Kong Lixia, Schneider Marlon R, Kirchner Thomas, Wolf Eckhard, Kolligs Frank T

机构信息

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.

Department of Medicine II, University of Munich, 81377 Munich, Germany.

出版信息

Biochem Biophys Res Commun. 2015 May 29;461(2):249-53. doi: 10.1016/j.bbrc.2015.04.009. Epub 2015 Apr 11.

DOI:10.1016/j.bbrc.2015.04.009

PMID:25869068

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.

摘要

在结直肠癌中经常发现，腺瘤性息肉病大肠杆菌（APC）肿瘤抑制基因失活后Wnt/β-连环蛋白信号通路失调。我们之前已经表明，位于肿瘤抑制基因位点18q21的β-连环蛋白靶基因ITF2编码的ITF-2B水平，在β-连环蛋白活性失调的结肠腺瘤中升高。然而，在肿瘤进展过程中，ITF-2B水平降低，这表明ITF-2B干扰肿瘤发展。为了研究ITF2在肠道肿瘤发生中的作用，我们在Apc(Min/+)小鼠的肠道上皮中特异性地使Itf2失活。我们发现，在Apc(Min/+)背景下Itf2的基因破坏导致更早死亡，并且小肠中的肿瘤数量和大小显著增加。基于这些数据，Itf2作为肠道的肿瘤抑制基因，抑制肿瘤起始和生长。