Enhanced expression of the type II transforming growth factor-β receptor is associated with decreased survival in human pancreatic cancer

Markus Wagner, Jörg Kleeff, Helmut Friess, Markus W. Büchler, Murray Korc

Research output: Contribution to journalArticlepeer-review

69 Scopus citations

Abstract

Transforming growth factor-βs (TGF-βs) bind to the type II TGF-β receptor (TβRII), which then heterodimerizes with the type I TGF-β receptor (TβRI), thereby initiating a signaling cascade. TGF-βs are overexpressed in pancreatic cancer, and this overexpression is associated with more aggressive disease. Although TβRII also is overexpressed in pancreatic ductal adenocarcinoma cells in vivo, the biologic significance of this overexpression is not completely known. Therefore in this study, we characterized TβRII expression by Northern blot analysis in 32 normal and 42 cancerous pancreatic tissues and correlated the survival of the cancer patients with TβRII messenger RNA (mRNA) levels. Northern blot analysis revealed that, by comparison with the normal controls, TβRII expression was increased in 19 (45%) of 42 cancer samples. Densitometric analysis of all the pancreatic tissues revealed a 3.4-fold increase (p < 0.01) in TβRII mRNA levels in the cancer tissues by comparison with normal controls. There was a strong correlation between the expression of TβRII and the levels of two invasion-promoting genes, plasminogen-activator-inhibitor-1 (PAI-1) and matrix-metalloproteinase-9 (MMP9). Log-rank analysis of the Kaplan-Meier survival curves indicated that patients whose tumors overexpressed TβRII had a significantly shorter survival period that did patients whose cancers expressed low levels of TβRII. It is suggested that TβRII overexpression may be a marker that correlates with disease progression in pancreatic ductal adenocarcinoma.

Original languageEnglish (US)
Pages (from-to)370-376
Number of pages7
JournalPancreas
Volume19
Issue number4
DOIs
StatePublished - Nov 1999

Keywords

  • MMP9
  • PAI-1
  • Pancreatic cancer
  • TGF-β receptor type II

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Hepatology
  • Endocrinology

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