ITF-2 Is Disrupted via Allelic Loss of Chromosome 18q21, and ITF-2B Expression Is Lost at the Adenoma-Carcinoma Transition

被引：21

作者：

Herbst, Andreas ^{[1
]}

Bommer, Guido T. ^{[1
]}

Kriegl, Lydia ^{[2
]}

Jung, Andreas ^{[2
]}

Behrens, Andrea ^{[1
]}

Csanadi, Endy ^{[1
]}

Gerhard, Markus ^{[3
]}

Bolz, Christian ^{[3
]}

Riesenberg, Rainer ^{[4
]}

Zimmermann, Wolfgang ^{[4
]}

Dietmaier, Wolfgang ^{[5
]}

Wolf, Isabella ^{[1
]}

Brabletz, Thomas ^{[6
]}

Goeke, Burkhard ^{[1
]}

Kolligs, Frank T. ^{[1
]}

机构：

[1] Univ Munich, Dept Med 2, D-81377 Munich, Germany

[2] Univ Munich, Dept Pathol, D-81377 Munich, Germany

[3] Tech Univ Munich, Dept Med 2, Munich, Germany

[4] Univ Munich, LIFE Ctr, Tumor Immunol Lab, Munich, Germany

[5] Univ Regensburg, Dept Pathol, Regensburg, Germany

[6] Univ Freiburg, Dept Visceral Surg, Freiburg, Germany

来源：

GASTROENTEROLOGY | 2009年 / 137卷 / 02期

关键词：

LOOP-HELIX PROTEINS; COLORECTAL-CANCER; CELL-CYCLE; BETA-CATENIN; P53; ARREST; GENE; P21; DCC; HYPERMETHYLATION;

D O I：

10.1053/j.gastro.2009.04.049

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

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.

引用

页码：639 / 648

页数：10

共 43 条

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