TY - JOUR
T1 - Induction of HDAC2 expression upon loss of APC in colorectal tumorigenesis
AU - Zhu, Ping
AU - Martin, Elke
AU - Mengwasser, Jörg
AU - Schlag, Peter
AU - Janssen, Klaus Peter
AU - Göttlicher, Martin
N1 - Funding Information:
The authors are thankful for technical support by M. Berauer, F. Kiefer, C. Leicht, M. Litfin, and C. Spiller. Animal experimentation was supported by S. Huber and N. Borel. D. Weih and M. Koch provided helpful advice for immunohistochemistry. Thanks to Thorsten Heinzel and Oliver Krämer, Georg-Speyer-Haus, Frankfurt, Germany for constructive discussions and sharing unpublished data. Drs. B. Vogelstein, K. Kinzler, E. Seto, and S.A. Kliewer are gratefully acknowledged for providing essential materials (HT29-APC cells, pcDNA/Myc-ΔN-hTcf4, pCMV-mRPD3-2.1, and mPPARδ cDNA, respectively). The study was supported by the Forschungszentrum Karlsruhe (fellowship to P.Z.) and the AICR, St. Andrews, UK (grant to M.G.). E.M. and J.M. are employees of G2M Cancer Drugs AG, which has a financial interest in inhibitors of histone deacetylases.
PY - 2004/5
Y1 - 2004/5
N2 - 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 Wnt 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 APCmin mice. These findings point toward HDAC2 as a particularly relevant potential target in cancer therapy.
AB - 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 Wnt 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 APCmin mice. These findings point toward HDAC2 as a particularly relevant potential target in cancer therapy.
UR - https://www.scopus.com/pages/publications/2342603414
U2 - 10.1016/S1535-6108(04)00114-X
DO - 10.1016/S1535-6108(04)00114-X
M3 - Article
C2 - 15144953
AN - SCOPUS:2342603414
SN - 1535-6108
VL - 5
SP - 455
EP - 463
JO - Cancer Cell
JF - Cancer Cell
IS - 5
ER -
