Histone deacetylase 1 is required for exocrine pancreatic epithelial proliferation in development and cancer

Weiqiang Zhou, I. Chau Liang, Nelson S. Yee

Research output: Contribution to journalArticle

22 Citations (Scopus)

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 upregulated 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.

Original languageEnglish (US)
Pages (from-to)659-670
Number of pages12
JournalCancer Biology and Therapy
Volume11
Issue number7
DOIs
StatePublished - Apr 1 2011

Fingerprint

Histone Deacetylase 1
Exocrine Pancreas
Histone Deacetylases
Pancreatic Neoplasms
Zebrafish
Neoplasms
Cell Cycle
Adenocarcinoma
Epithelium
Cell Proliferation
Hedgehogs
Cyclin-Dependent Kinases
RNA Interference
Morphogenesis
Epigenomics
Cell Line
Mutation
Growth
Genes

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Oncology
  • Pharmacology
  • Cancer Research

Cite this

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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 upregulated 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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Histone deacetylase 1 is required for exocrine pancreatic epithelial proliferation in development and cancer. / Zhou, Weiqiang; Liang, I. Chau; Yee, Nelson S.

In: Cancer Biology and Therapy, Vol. 11, No. 7, 01.04.2011, p. 659-670.

Research output: Contribution to journalArticle

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