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

Int J Cancer. 1998 Sep 11;77(6):860-8. doi: 10.1002/(sici)1097-0215(19980911)77:6<860::aid-ijc11>;2-5.


Activins and inhibins belong to the transforming growth factor-beta (TGF-beta) 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 (betaA, betaB, alpha), 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-1, CAPAN-1, COLO-357, MIA-PaCa-2, PANC-1 and T3M4) expressed the activin/inhibin betaA subunit, whereas expression levels of the activin/inhibin betaB and alpha subunits were undetectable. Furthermore, actRI, actRII and actRIIb were expressed in all cell lines and actRIb mRNA was evident in ASPC-1, CAPAN-1, COLO-357 and PANC-1 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-1, COLO-357 and MIA-PaCa-2 cells. Pancreatic cancer samples markedly over-expressed the activin/inhibin betaA subunit, whereas the betaB 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 betaA, 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Activin Receptors
  • Activins
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Blotting, Northern
  • Carcinoma, Ductal, Breast / metabolism*
  • Cell Differentiation
  • DNA Primers
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • In Situ Hybridization
  • In Vitro Techniques
  • Inhibins / metabolism*
  • Male
  • Middle Aged
  • Pancreatic Neoplasms / metabolism*
  • Polymerase Chain Reaction
  • Receptors, Growth Factor / metabolism*
  • Receptors, Peptide / metabolism*
  • Tumor Cells, Cultured / metabolism
  • Up-Regulation


  • DNA Primers
  • Receptors, Growth Factor
  • Receptors, Peptide
  • Activins
  • Inhibins
  • Activin Receptors