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

Research output: Contribution to journalArticle

42 Citations (Scopus)

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, and 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, and in so doing appear to co-opt a normal cellular mechanism for the regulation of this gene.

Original languageEnglish (US)
Pages (from-to)427-436
Number of pages10
JournalNeoplasia
Volume5
Issue number5
StatePublished - Sep 2003

Fingerprint

Epigenomics
Histones
Pancreas
decitabine
Pancreatic Carcinoma
SERPIN-B5
Genes
Cell Line
Chromatin Immunoprecipitation
Cytosine
Methylation
Carcinogenesis
Maintenance

Keywords

  • Cancer
  • DNA methylation
  • Gene expression
  • Histone acetylation
  • Tumor suppressor gene

ASJC Scopus subject areas

  • Cancer Research

Cite this

Fitzgerald, M., Oshiro, M., Holtan, N., Krager, K., Cullen, J. J., Futscher, B. W., & Domann, F. E. (2003). Human Pancreatic Carcinoma Cells Activate Maspin Expression Through Loss of Epigenetic Control. Neoplasia, 5(5), 427-436.

Human Pancreatic Carcinoma Cells Activate Maspin Expression Through Loss of Epigenetic Control. / Fitzgerald, Matthew; Oshiro, Marc; Holtan, Nicholas; Krager, Kimberly; Cullen, Joseph J.; Futscher, Bernard W; Domann, Frederick E.

In: Neoplasia, Vol. 5, No. 5, 09.2003, p. 427-436.

Research output: Contribution to journalArticle

Fitzgerald, M, Oshiro, M, Holtan, N, Krager, K, Cullen, JJ, Futscher, BW & Domann, FE 2003, 'Human Pancreatic Carcinoma Cells Activate Maspin Expression Through Loss of Epigenetic Control', Neoplasia, vol. 5, no. 5, pp. 427-436.
Fitzgerald M, Oshiro M, Holtan N, Krager K, Cullen JJ, Futscher BW et al. Human Pancreatic Carcinoma Cells Activate Maspin Expression Through Loss of Epigenetic Control. Neoplasia. 2003 Sep;5(5):427-436.
Fitzgerald, Matthew ; Oshiro, Marc ; Holtan, Nicholas ; Krager, Kimberly ; Cullen, Joseph J. ; Futscher, Bernard W ; Domann, Frederick E. / Human Pancreatic Carcinoma Cells Activate Maspin Expression Through Loss of Epigenetic Control. In: Neoplasia. 2003 ; Vol. 5, No. 5. pp. 427-436.
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