CONCOMITANT OVER-EXPRESSION OF ACTIVIN INHIBIN BETA-SUBUNITS AND THEIR RECEPTORS IN HUMAN PANCREATIC-CANCER/

Activins and inhibins belong to the transforming growth factor-beta (T GF-beta) superfamily of multifunctional cytokines that bind to transme mbrane receptors with serine/threonine kinase activity. In this study, we characterized the levels of expression of 3 activin/inhibin subuni ts (beta A, beta B, alpha), and 2 type I and type II activin receptors (actRI/Ib, actRII/IIb) in pancreatic cancer cell lines and in human p ancreatic tissues. In addition, we assessed the growth responsiveness to activin A in these cell lines. All 6 cell lines (ASPC-I, CAPAN-I, C OLO-357, MIA-PaCa-2, PANG-I and T3M4) expressed the activin/inhibin be ta A subunit, whereas expression levels of the activinlinhibin beta B and or subunits were undetectable. Furthermore, actRI, actRII and actR IIb were expressed in all cell lines and actRIb mRNA was evident in AS PC-I, CAPAN- I, COLO-357 and PANG-I cells. CAPAN-I and COLO-357 cells were growth-stimulated by activin A in the presence of 10% serum, wher eas 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-expresse d the activin/inhibin beta A subunit, whereas the beta B subunit was o nly moderately increased in comparison to normal pancreatic samples. P ancreatic cancer tissues also markedly over-expressed actRI, actRIb an d actRII. By in site hybridization, activinlinhibin beta A, actRI, act RIb and actRII were strongly expressed in diffuse infiltrative and duc t-like cancer cells. Both the ligand and its receptors were often co-e xpressed in these cells. Together, our findings suggest that activin A may participate in autocrine activation of pancreatic cancer cells in vivo. (C) 1998 Wiley-Liss, Inc.