Human Pancreatic Carcinoma Cells Activate Maspin Expression Through Loss of Epigenetic Control

Matthew Fitzgerald; Marc Oshiro; Nicholas Holtan; Kimberly Krager; Joseph J Cullen; Bernard W Futscher; Frederick E Domann

doi:10.1016/S1476-5586(03)80045-3

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Human Pancreatic Carcinoma Cells Activate Maspin Expression Through Loss of Epigenetic Control

Journal article

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Human Pancreatic Carcinoma Cells Activate Maspin Expression Through Loss of Epigenetic Control

Matthew Fitzgerald, Marc Oshiro, Nicholas Holtan, Kimberly Krager, Joseph J Cullen, Bernard W Futscher and Frederick E Domann

Neoplasia (New York, N.Y.), Vol.5(5), pp.427-436

09/2003

DOI: 10.1016/S1476-5586(03)80045-3

PMID: 14670180

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Abstract

The maspin gene is not expressed in normal human pancreas, but its expression is acquired during human pancreatic carcinogenesis. In other normal human cells and their malignant counterparts, maspin expression is controlled through the epigenetic state of its promoter. In studies presented herein, we used bisulfite genomic sequencing and chromatin immunoprecipitation studies to show that maspin-negative pancreas cells have a methylated maspin promoter, that the associated H3 and H4 histones are hypoacetylated. In contrast to normal pancreas, four of six human pancreatic carcinoma cell lines investigated displayed activation of maspin expression. This activation of maspin expression in pancreatic carcinoma cells was linked to demethylated promoters and hyperacetylation of the associated H3 and H4 histones. In addition, 5-aza-2′-deoxycytidine treatments activated maspin expression in the two maspin-negative pancreatic carcinoma cell lines, suggesting a causal role for cytosine methylation in the maintenance of a transcriptionally silent maspin gene. Thus, human pancreatic carcinoma cells acquire maspin expression through epigenetic derepression of the maspin locus, in so doing appear to co-opt a normal cellular mechanism for the regulation of this gene.

DNA methylation

cancer

histone acetylation

tumor suppressor gene

gene expression

Details

Title: Subtitle: Human Pancreatic Carcinoma Cells Activate Maspin Expression Through Loss of Epigenetic Control
Creators: Matthew Fitzgerald - Department of Radiation Oncology, Free Radical and Radiation Biology Program, University of Iowa, Iowa City, IA 52242, USA
Marc Oshiro - Department of Pharmacology and Toxicology, Bone Marrow Transplant Program, Arizona Cancer Center, The University of Arizona, Tucson, AZ 85724, USA
Nicholas Holtan - Department of Pharmacology and Toxicology, Bone Marrow Transplant Program, Arizona Cancer Center, The University of Arizona, Tucson, AZ 85724, USA
Kimberly Krager - Department of Radiation Oncology, Free Radical and Radiation Biology Program, University of Iowa, Iowa City, IA 52242, USA
Joseph J Cullen - Department of Surgery, University of Iowa, Iowa City, IA 52242, USA
Bernard W Futscher - Department of Pharmacology and Toxicology, Bone Marrow Transplant Program, Arizona Cancer Center, The University of Arizona, Tucson, AZ 85724, USA
Frederick E Domann - Department of Radiation Oncology, Free Radical and Radiation Biology Program, University of Iowa, Iowa City, IA 52242, USA
Resource Type: Journal article
Publication Details: Neoplasia (New York, N.Y.), Vol.5(5), pp.427-436
DOI: 10.1016/S1476-5586(03)80045-3
PMID: 14670180
NLM abbreviation: Neoplasia
ISSN: 1476-5586
eISSN: 1476-5586
Publisher: Elsevier Inc
Language: English
Date published: 09/2003
Academic Unit: Pathology; Surgery; Radiation Oncology
Record Identifier: 9984047712402771

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