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

✍ Scribed by Jörg Kleeff; Toshiyuki Ishiwata; Helmut Friess; Markus W. Büchler; Murray Korc

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: French
• Weight: 355 KB
• Volume: 77
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/(sici)1097-0215(19980911)77:6<860::aid-ijc11>3.0.co;2-5

✦ Synopsis

Activins and inhibins belong to the transforming growth factor-␤ (TGF-␤) 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 (␤A, ␤B, ␣), 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 ␤A subunit, whereas expression levels of the activin/inhibin ␤B and ␣ 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-1 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 ␤A subunit, whereas the ␤B 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 ␤A, 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.