Induction of HDAC2 expression upon loss of APC in colorectal tumorigenesis

被引:437
作者
Zhu, P
Martin, E
Mengwasser, J
Schlag, P
Janssen, KP
Göttlicher, M
机构
[1] Forschungszentrum Karlsruhe, Inst Toxicol & Genet, D-76344 Eggenstein, Germany
[2] G2M Canc Drugs AG, D-76344 Eggenstein, Germany
[3] Robert Rossle Klin, D-13125 Berlin, Germany
[4] Tech Univ Munich, Dept Surg, D-81675 Munich, Germany
[5] GSF, Natl Res Ctr Environm & Hlth, Inst Toxicol, D-85764 Neuherberg, Germany
关键词
D O I
10.1016/S1535-6108(04)00114-X
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Inappropriate transcriptional repression involving histone deacetylases (HDACs) is a prominent cause for the development of leukemia. We now identify faulty expression of a specific mediator of transcriptional repression in a solid tumor. Loss of the adenomatosis polyposis coli (APC) tumor suppressor induces HDAC2 expression depending on the Writ pathway and c-Myc. Increased HDAC2 expression is found in the majority of human colon cancer explants, as well as in intestinal mucosa and polyps of APC-deficient mice. HDAC2 is required for, and sufficient on its own to prevent, apoptosis of colonic cancer cells. Interference with HDAC2 by valproic acid largely diminishes adenoma formation in ApC(min) mice. These findings point toward HDAC2 as a particularly relevant potential target in cancer therapy.
引用
收藏
页码:455 / 463
页数:9
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