ZFIN ID: ZDB-PUB-110214-16
Histone deacetylase 1 is required for exocrine pancreatic epithelial proliferation in development and cancer
Zhou, W., Liang, I.C., and Yee, N.
Date: 2011
Source: Cancer biology & therapy   11(7): 659-70 (Journal)
Registered Authors: Yee, Nelson S.
Keywords: none
MeSH Terms:
  • Acetylation
  • Adenocarcinoma/enzymology*
  • Adenocarcinoma/genetics
  • Adenocarcinoma/pathology
  • Animals
  • Cell Differentiation/genetics
  • Cell Line
  • Cell Proliferation
  • Epithelial Cells/cytology*
  • Epithelial Cells/enzymology*
  • Epithelial Cells/pathology
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental
  • Gene Expression Regulation, Neoplastic
  • Histone Deacetylase 1/genetics
  • Histone Deacetylase 1/metabolism*
  • Histones/metabolism
  • Humans
  • Models, Animal
  • Pancreas, Exocrine/cytology
  • Pancreas, Exocrine/enzymology*
  • Pancreatic Neoplasms/enzymology*
  • Pancreatic Neoplasms/genetics
  • Pancreatic Neoplasms/pathology
  • RNA Interference
  • Signal Transduction
  • Zebrafish
PubMed: 21301206 Full text @ Cancer Biol. Ther.
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ABSTRACT
Histone deacetylases (HDACs) play important roles in the epigenetic control of development, and aberrant expression of HDACs has been implicated in human diseases including cancer. Among the mammalian HDACs, HDAC1 has been extensively studied, but its role in exocrine pancreatic morphogenesis and cancer is still poorly understood. The goal of this study is to determine the functional role of HDAC1 in normal development of exocrine pancreas using zebrafish as the model organism as well as in human pancreatic adenocarcinoma. The zebrafish germline loss-of-function mutation hdac1hi1618 caused impaired cell cycle progression in pancreatic epithelia, resulting in growth arrest and dysmorphogenesis of exocrine pancreas. In human pancreatic adenocarcinoma tissues and cell lines, HDAC1 was expressed at variably elevated levels. RNA interference-induced silencing of HDAC1 diminished proliferation of the cancer cells and cell cycle progression. The proliferative arrest in the developing exocrine pancreas and pancreatic cancer cells was associated with up-regulated expression of the cyclin-dependent kinase inhibitors and the sonic hedgehog signaling components. This study indicates that HDAC1 is required for pancreatic epithelial proliferation in development and cancer. We hypothesize that aberrant expression of HDAC1 modulates the developmental and signaling pathways in exocrine pancreatic epithelia and consequently the genes required for cellular proliferation during development and progression of pancreatic neoplasia.
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