@article{17593101bd724ba1bb1362291d2604a5,
title = "Histone deacetylase 1 is required for exocrine pancreatic epithelial proliferation in development and cancer",
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.",
author = "Weiqiang Zhou and Liang, {I. Chau} and Yee, {Nelson S.}",
note = "Funding Information: siRNA-treated or control cells, was extracted and reverse tran-The authors wish to acknowledge the Tissue Procurement Core scribed. The relative levels of p21CDKN1A, p27CDKN1B, HHIP and Facility, Comparative Pathology Laboratory, DNA Facility and SMO mRNA were determined relative to GAPDH as described Flow Cytometry Facility of the University of Iowa for techni-in reference 46. The sequences of the primers used are based on cal support and equipments. This work is supported by the Pilot human cDNA sequences of p21CDKN1A, p27CDKN1B, HHIP, SMO Grant in Translational Research by the Department of Internal and GAPDH (NCBI accession number NM_000389, BC001971, Medicine of the University of Iowa Carver College of Medicine NM_022475, U84401, NM_002046, respectively): (N.S.Y.), the Holden Comprehensive Cancer Center Designated p21CDKN1A: 5'-ATG CAG CTC CAG ACA GAT GA-3', Gift Fund for pancreatic cancer research (N.S.Y.) and the Cancer 5'-CGC AAA CAG ACC AAC ATC AC-3' Center Support Grant (P30 CA 086862) by the National p27CDKN1B: 5'-TGA AGC CTG GAA CTT CGA CT-3', Cancer Institute to the Holden Comprehensive Cancer Center 5'-TGT GAA TAT CGG AGC CCT TC-3' of the University of Iowa (N.S.Y.). The Zebrafish International HHIP: 5'-GCA GAG GAG ACC TCA GCA TC-3', 5'-GCA Resource Center is supported by grant P40 RR12546 from the GTT GTG CCA GTG TCA GT-3' NIH-NCRR. SMO: 5'-TCA CTC CCC TTT GTC CTC AC-3', 5'-TGG TCT CGT TGA TCT TGC TG-3' Note GAPDH: 5'-GAG TCA ACG GAT TTG GTC GT-3', 5'-TTG Supplemental materials can be found at: ATT TTG GAG GGA TCT CG-3'. www.landesbioscience.com/journals/cbt/article/14720",
year = "2011",
month = apr,
day = "1",
doi = "10.4161/cbt.11.7.14720",
language = "English (US)",
volume = "11",
pages = "659--670",
journal = "Cancer Biology and Therapy",
issn = "1538-4047",
publisher = "Landes Bioscience",
number = "7",
}