Concomitant over-expression of activin/inhibin β subunits and their receptors in human pancreatic cancer

Jörg Kleeff, Toshiyuki Ishiwata, Helmut Friess, Markus W. Búchler, Murray Korc

Research output: Contribution to journalArticlepeer-review

57 Scopus citations

Abstract

Activins and inhibins belong to the transforming growth factor-β (TGF- β) superfamily of multifunctional cytokines that bind to transmembrane receptors with serine/threonine kinase activity. In this study, we characterized the levels of expression of 3 activin/inhibin subunits (βA, βB, α), and 2 type I and type II activin receptors (actRI/Ib, actRII/IIb) in pancreatic cancer cell lines and in human pancreatic tissues. In addition, we assessed the growth responsiveness to activin A in these cell lines. All 6 cell lines (ASPC-I, CAPAN-I, COLO-3S7, MIA-PaCa-2, PANC-I and T3M4) expressed the activin/inhibin βA subunit, whereas expression levels of the activin/inhibin βB and α subunits were undetectable. Furthermore, actRI, actRII and actRIIb were expressed in all cell lines and actRib mRNA was evident in ASPC-I, CAPAN-I, COLO357 and PANC-I cells. CAPAN-I and COLO-357 cells were growth-stimulated by activin A in the presence of 10% serum, whereas the other cell lines were resistant to activin A. In contrast, in serum-free medium activin A inhibited the growth of CAPAN-I, COLO-357 and MIA-PaCa-2 cells. Pancreatic cancer samples markedly over-expressed the activin/inhibin βA subunit, whereas the βB subunit was only moderately increased in comparison to normal pancreatic samples. Pancreatic cancer tissues also markedly over-expressed actRI, actRib and actRII. By in situ hybridization, activin/inhibin βA, actRI, actRIb and actRII were strongly expressed in diffuse infiltrative and duct-like cancer cells. Both the ligand and its receptors were often co-expressed in these cells. Together, our findings suggest that activin A may participate in autocrine activation of pancreatic cancer cells in vivo.

Original languageEnglish (US)
Pages (from-to)860-868
Number of pages9
JournalInternational Journal of Cancer
Volume77
Issue number6
DOIs
StatePublished - 1998

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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