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Smad6 suppresses TGF-β-induced growth inhibition in COLO-357 pancreatic cancer cells and is overexpressed in pancreatic cancer

被引：94
作者：
Kleeff, J
Maruyama, H
Friess, H
Büchler, MW
Falb, D
Korc, M
机构：
[1] Univ Calif Irvine, Div Endocrinol Diabet & Metab, Irvine, CA 92697 USA
[2] Univ Calif Irvine, Dept Biol Chem, Irvine, CA 92697 USA
[3] Univ Calif Irvine, Dept Pharmacol, Irvine, CA 92697 USA
[4] Univ Bern, Dept Visceral & Transplantat Surg, CH-3010 Bern, Switzerland
[5] Millennium Pharmaceut, Cambridge, MA 02139 USA
[6] Univ Calif Irvine, Dept Med, Irvine, CA 92697 USA
来源：
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 1999年 / 255卷 / 02期
关键词：
Smad6; pancreas; cancer; TGF-beta;
D O I：
10.1006/bbrc.1999.0171
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Transforming growth factor (TGF)-beta signaling is initiated by heterodimerization of TGF-beta receptor type I (T beta RI) and type II (T beta RII). Subsequently, the signal is transduced via Smad proteins, which upon phosphorylation and heterodimerization translocate to the nucleus and regulate gene transcription. Smad6 functions as an intracellular antagonist of TGF-beta signaling. In the present study we demonstrate that Smad6 is overexpressed in vivo in human pancreatic cancer cells. We also show that stable transfection of a full-length Smad6 construct into COLO-357 pancreatic cancer cells abrogates TGF-beta 1 induced growth inhibition, and leads to enhanced anchorage-independent growth. Thus, enhanced expression of the TGF-beta signaling inhibitor Smad6 in pancreatic cancer may present a novel mechanism of TGF-beta resistance, which might have the potential to enhance the transformed phenotype of human cancer cells. (C) 1999 Academic Press.
引用
收藏
页码：268 / 273
页数：6
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