Clinicopathological significance and molecular regulation of maspin expression in ductal adenocarcinoma of the pancreas

Nobuyuki Ohike, Nicolai Maass, Christoph Mundhenke, Marco Biallek, Ming Zhang, Walter Jonat, Jutta Lüttges, Toshio Morohoshi, Günter Klöppel, Koichi Nagasaki*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

We evaluated the biological relevance of maspin expression in pancreatic ductal adenocarcinoma and studied regulatory mechanisms of maspin gene activation in pancreatic carcinoma cell lines. Maspin expression was immunohistochemically detected in a series of 57 pancreatic ductal adenocarcinomas, 51 (90%) of which were classified as high-expressers. In lymph node metastases, maspin expression was somewhat decreasingly found in 39/49 (80%). Maspin high-expressers showed predominantly a low histological grade (p=0.013). Moreover, maspin expression was found in two mixed ductal-endocrine carcinomas, but not in 10 endocrine tumors and the surrounding normal pancreatic tissues. Using a luciferase reporter system, maspin promoter activity was induced in the maspin-positive pancreatic cancer cell lines as well as maspin-negative PANC-1 cells. Additionally, treatment with the DNA methyltransferase inhibitor, 5-aza-2′ deoxycytidine, and histone deacetylase inhibitor, trichostatin A, led to re-expression of maspin mRNA in PANC-1 cells. Our results indicate that maspin expression is up-regulated in most if not all pancreatic ductal adenocarcinomas and may be related to the development and differentiation, and that DNA methylation and histone deacetylation may suppress maspin gene activation in pancreatic cancer cells.

Original languageEnglish (US)
Pages (from-to)193-200
Number of pages8
JournalCancer Letters
Volume199
Issue number2
DOIs
StatePublished - Sep 25 2003

Keywords

  • DNA methylation
  • Histone deacetylation
  • Maspin
  • Pancreatic ductal adenocarcinoma
  • Tumor suppressor gene

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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