Rl. Baldwin et al., ATTENUATED ALK5 RECEPTOR EXPRESSION IN HUMAN PANCREATIC-CANCER - CORRELATION WITH RESISTANCE TO GROWTH-INHIBITION, International journal of cancer, 67(2), 1996, pp. 283-288
Transforming growth factor-beta (TGF-beta) receptors constitute a fami
ly of transmembrane proteins that bind TGF-beta ligands. In this study
we assessed the growth responsiveness to TGF-beta 1 in pancreatic can
cer cell lines and characterized the levels of expression of TGF-beta
receptors in these cell lines and in human pancreatic cancer tissues.
COLO 357 cells were most sensitive to the growth inhibitory actions of
TGF-beta 1, PANC-1 cells exhibited moderate sensitivity, Hs766T cells
exhibited slight sensitivity and MIA PaCa-2 and T3M4 cells were resis
tant to TGF-beta 1. Only COLO 357 cells expressed high levels of ALK5,
the major type I TGF-beta receptor (T beta RI). Hs766T and PANC-1 cel
ls expressed high levels of SKR1, another T beta RI subtype. Only MIA
PaCa-2 cells did not exhibit the type II TGF-beta receptor (T beta-RII
) transcript, whereas type III TGF-beta receptor (T beta-RIII) mRNA le
vels were elevated in this cell line and in HS766T cells. All the cell
lines expressed TGF-beta 1, but TGF-beta 2 and TGF-beta 3 mRNA levels
were variable. ALK5 and SKR1 mRNA levels were 6.8- and 9-fold greater
in the pancreatic tumors in comparison with the corresponding levels
in the normal pancreas. However, in the cancer cells, ALK5 immunoreact
ivity was faint, whereas T beta RII immunoreactivity was focal and int
ense. Conversely, in ductal cells adjacent to cancer cells ALK5 immuno
reactivity was strong, whereas T beta RII immunoreactivity was weak. S
ince ALK5 heterodimerization with T beta RII is crucial for TGF-beta-m
ediated signaling, our findings suggest that low levels of ALK5 in pan
creatic cancer cells within a tumor may protect against growth inhibit
ion. (C) 1996 Wiley-Liss, Inc.