Induction and expression of ßig-h3 in pancreatic cancer cells

Dominik Schneider, Jörg Kleeff, Pascal O. Berberat, Zhaowen Zhu, Murray Korc, Helmut Friess, Markus W. Büchler

Research output: Contribution to journalArticle

52 Scopus citations

Abstract

ßig-h3 (TGFBI, keratoepithelin) was first identified as a transforming growth factor-β1 (TGF-β1)-inducible gene in a human lung adenocarcinoma cell line. It encodes for a secreted extracellular matrix (ECM) protein, which is thought to act on cell attachment and ECM composition. Mutations of the ßig-h3 gene are involved in several corneal dystrophies. Pancreatic cancers display multiple alterations in the TGF-β signaling pathway and in TGF-β response genes, such as overexpression of all three TGF-β isoforms and Smad4 mutations. In this report, we determined that ßig-h3 mRNA levels were induced by TGF-β1 in two out of five examined pancreatic cancer cell lines (CAPAN-1, PANC-1). In CAPAN-1 cells, which harbor a Smad4 mutation, ßig-h3 but not PAI-1 was induced by TGF-β1, whereas in PANC-1 cells that express wild-type Smad4, TGF-β1 induced both PAI-1 and ßig-h3. In human pancreatic tissues, there was a 32.4-fold increase in ßig-h3 mRNA levels in pancreatic cancers in comparison to normal control tissues. In situ hybridization analysis revealed that ßig-h3 mRNA was expressed mainly in the cancer cells within the pancreatic tumor mass. These findings suggest that ßig-h3 is induced by TGF-βs in pancreatic cancer cells even in the presence of Smad4 mutations, which might explain, in part, the increased ßig-h3 mRNA levels observed in pancreatic cancer cells in vivo.

Original languageEnglish (US)
Pages (from-to)1-6
Number of pages6
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1588
Issue number1
DOIs
StatePublished - Oct 9 2002

Keywords

  • PAI-1
  • Pancreatic cancer
  • SMAD4
  • TGF-β
  • ßig-h3

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology

Fingerprint Dive into the research topics of 'Induction and expression of ßig-h3 in pancreatic cancer cells'. Together they form a unique fingerprint.

  • Cite this

    Schneider, D., Kleeff, J., Berberat, P. O., Zhu, Z., Korc, M., Friess, H., & Büchler, M. W. (2002). Induction and expression of ßig-h3 in pancreatic cancer cells. Biochimica et Biophysica Acta - Molecular Basis of Disease, 1588(1), 1-6. https://doi.org/10.1016/S0925-4439(02)00052-2