Overexpression of Smad2 and colocalization with TGF-β1 in human pancreatic cancer

Jörg Kleeff, Helmut Friess, Peter Simon, Sergio Susmallian, Peter Büchler, Arthur Zimmermann, Markus W. Büchler, Murray Korc

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Smad2 belongs to a family of cytoplasmic molecules that are critical components in the transforming growth factor β (TGF-β) signaling pathway. Upon ligand binding, the type II TGF-β receptor (TβRII) heterodimerizes with and activates TGF-β receptor type I (TβRI). Activated TβRI phosphorylates Smad2, which then heterodimerizes with Smad4, translocates into the nucleus, and subsequently effects gene transcription. Previously we have shown that pancreatic cancers overexpress TGF-βs and TβRII. Here, we show by northern blot analysis that Smad2 mRNA levels are significantly increased in pancreatic cancer samples in comparison with normal pancreatic tissues. By immunohistochemistry, Smad2 is present in the cancer cells of 67% of the pancreatic cancer samples. Analysis of serial sections reveals coexpression of Smad2 and TGF-β1 in the cancer cells. Furthermore, TGF-β1 increases steady-state levels of Smad2 mRNA in the TGF-β1-sensitive pancreatic cancer cell line COLO-357. It is suggested that pancreatic cancer cells have the capacity to up-regulate Smad2 expression, which may lead to excessive activation of specific components of the TGF-β-signaling pathway.

Original languageEnglish (US)
Pages (from-to)1793-1802
Number of pages10
JournalDigestive diseases and sciences
Volume44
Issue number9
DOIs
StatePublished - Oct 1 1999

Keywords

  • Cancer
  • Pancreas
  • Smad2
  • TGF-β

ASJC Scopus subject areas

  • Physiology
  • Gastroenterology

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    Kleeff, J., Friess, H., Simon, P., Susmallian, S., Büchler, P., Zimmermann, A., Büchler, M. W., & Korc, M. (1999). Overexpression of Smad2 and colocalization with TGF-β1 in human pancreatic cancer. Digestive diseases and sciences, 44(9), 1793-1802. https://doi.org/10.1023/A:1018882320500