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 (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.
Department of Medicine, University of California, Irvine 92697, USA.
J
J
Kleeff
T
T
Ishiwata
H
H
Friess
M W
MW
Büchler
M
M
Korc
D029404:Activin Receptors; D028341:Activins; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015152:Blotting, Northern; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism*; D002454:Cell Differentiation; D017931:DNA Primers; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017403:In Situ Hybridization; D066298:In Vitro Techniques; D007265:Inhibins / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D017978:Receptors, Growth Factor / Q000378:metabolism*; D018000:Receptors, Peptide / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000378:metabolism; D015854:Up-Regulation
D017931:DNA Primers; D017978:Receptors, Growth Factor; D018000:Receptors, Peptide; D028341:Activins; D007265:Inhibins; D029404:Activin Receptors