PUBLICATION
Histone deacetylase 1 is required for exocrine pancreatic epithelial proliferation in development and cancer
- Authors
- Zhou, W., Liang, I.C., and Yee, N.
- ID
- ZDB-PUB-110214-16
- Date
- 2011
- Source
- Cancer biology & therapy 11(7): 659-70 (Journal)
- Registered Authors
- Yee, Nelson S.
- Keywords
- none
- MeSH Terms
-
- Humans
- Pancreatic Neoplasms/enzymology*
- Pancreatic Neoplasms/genetics
- Pancreatic Neoplasms/pathology
- Gene Expression Profiling
- Cell Proliferation
- Models, Animal
- Epithelial Cells/cytology*
- Epithelial Cells/enzymology*
- Epithelial Cells/pathology
- Cell Differentiation/genetics
- Gene Expression Regulation, Developmental
- Gene Expression Regulation, Neoplastic
- Pancreas, Exocrine/cytology
- Pancreas, Exocrine/enzymology*
- Histone Deacetylase 1/genetics
- Histone Deacetylase 1/metabolism*
- Zebrafish
- Histones/metabolism
- Adenocarcinoma/enzymology*
- Adenocarcinoma/genetics
- Adenocarcinoma/pathology
- Animals
- Acetylation
- Cell Line
- RNA Interference
- Signal Transduction
- PubMed
- 21301206 Full text @ Cancer Biol. Ther.
Citation
Zhou, W., Liang, I.C., and Yee, N. (2011) Histone deacetylase 1 is required for exocrine pancreatic epithelial proliferation in development and cancer. Cancer biology & therapy. 11(7):659-70.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping