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

Abstract

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.

• Authors: J Kleeff, T Ishiwata, H Friess, M W Büchler, M Korc
• Journal: International journal of cancer (Int J Cancer) Vol. 77 Issue 6 Pg. 860-8 (Sep 11 1998) ISSN: 0020-7136 [Print] United States
• PMID: 9714055 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

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

Topics

• 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