HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

HDAC3 overexpression and colon cancer cell proliferation and differentiation.

Abstract
An immunohistochemical analysis of human colorectal adenocarcinomas showed that cancer cells express widely varying levels of HDAC3. The SW480 colon cancer cell line was found to express high levels of HDAC3 compared to other colon cancer cell lines. p21 was poorly induced in SW480 cells relative to the lower HDAC3-expressing HT-29 cells. RNAi-induced reduction of HDAC3 in SW480 cells increased their constitutive, butyrate-, TSA-, and TNF-alpha-induced expression of p21, but did not cause all the gene expression changes induced upon general histone deacetylase (HDAC) inhibition. SW480 cells with lower HDAC3 expression appeared to be poised for gene expression responses with increased histone H4-K12 acetylation, but not K5, K8, or K16 acetylation. Even though p21 was readily activated in HT29 cells, HDAC3 siRNA nonetheless stimulated p21 expression in these cells to a greater degree than HDAC1 and HDAC2 siRNA. SW480 cells with lower HDAC3 levels displayed an enhanced cell cycle arrest and growth inhibition by butyrate, but without changes in apoptosis or sensitivity to chemotherapeutic agents. As reported for other colon cancer cell lines, butyrate induced the rapid downregulation of the secretory cell differentiation markers mucin 2 and intestinal trefoil factor in SW480 cells. Interestingly, selective HDAC3 inhibition was sufficient to downregulate these genes. Our data support a central role for HDAC3 in regulating the cell proliferation and differentiation of colon cancer cells and suggest a potential mechanism by which colon cancers may become resistant to luminal butyrate.
AuthorsColleen C Spurling, Cassandra A Godman, Emily J Noonan, Theodore P Rasmussen, Daniel W Rosenberg, Charles Giardina
JournalMolecular carcinogenesis (Mol Carcinog) Vol. 47 Issue 2 Pg. 137-47 (Feb 2008) ISSN: 1098-2744 [Electronic] United States
PMID17849419 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Copyright(c) 2007 Wiley-Liss, Inc.
Chemical References
  • DNA Primers
  • Histones
  • Histone Deacetylases
  • histone deacetylase 3
Topics
  • Acetylation
  • Adenocarcinoma (enzymology, pathology)
  • Apoptosis
  • Base Sequence
  • Cell Differentiation
  • Cell Line, Tumor
  • Cell Proliferation
  • Colorectal Neoplasms (enzymology, pathology)
  • DNA Primers
  • Histone Deacetylases (metabolism)
  • Histones (metabolism)
  • Humans
  • Immunohistochemistry
  • Reverse Transcriptase Polymerase Chain Reaction

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: