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Concomitant over‐expression of activin/inhibin β subunits and their receptors in human pancreatic cancer
Author(s) -
Kleeff Jörg,
Ishiwata Toshiyuki,
Friess Helmut,
Büchler Markus W.,
Korc Murray
Publication year - 1998
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19980911)77:6<860::aid-ijc11>3.0.co;2-5
Subject(s) - activin receptor , acvr2b , activin type 2 receptors , endocrinology , medicine , pancreatic cancer , receptor , tgf beta signaling pathway , biology , transforming growth factor , chemistry , cancer
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‐1, CAPAN‐1, COLO‐357, MIA‐PaCa‐2, PANC‐1 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‐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 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 . Int. J. Cancer 77:860–868, 1998.© 1998 Wiley‐Liss, Inc.