Ligand Induced Upregulation of the Type II Transforming Growth Factor (TGF-[beta]) Receptor Enhances TGF-P Responsiveness in COLO-357 Cells.
Kleeff, Jorg; Wildi, Stefan; Fries, Helmut *; Korc, Murray
18(4):364-370, May 1999.
(Format: HTML, PDF)
Summary: The effects of transforming growth factor (TGF)-[beta]1 on type I and type II TGF-[beta] receptor (T[beta]RI and T[beta]RII) expression were examined in five pancreatic cancer cell lines. In contrast to its actions in COLO-357, a TGF-[beta]-sensitive pancreatic cancer cell line, TGF-[beta]1 did not significantly alter TGF-[beta] receptor expression in either the TGF-[beta]-sensitive BXPC-3 and PANC-1 cells or in the TGF-[beta]-resistant CAPAN-1 and T3M4 cells. Neutralizing anti-T[beta]RII antibodies blocked TGF-[beta]1-dependent signaling in COLO-357 cells but exhibited an attenuated effect in COLO-357 cells preincubated with TGF-[beta]1 for 48 h. Basal T[beta]RII expression levels were comparable in all five cell lines examined. In contrast, COLO-357 cells and BX-PC-3 cells expressed relatively high basal levels of T[beta]RI. However, COLO-357 cells harbored a normal Smad4 gene, whereas BX-PC-3 cells exhibited a complete deletion of this gene. We conclude that the TGF-[beta]1-induced T[beta]RII upregulation serves to enhance TGF-[beta]1 responsiveness in COLO-357 cells, and that this upregulation requires the presence of adequate levels of T[beta]RI and T[beta]RII, and a functional Smad4 gene product. Our findings also indicate that TGF-[beta]1 may inhibit pancreatic cancer cell growth via a Smad4-independent pathway.
(C) 1999 Lippincott Williams & Wilkins, Inc.