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Smad6 Suppresses TGF-β-Induced Growth Inhibition in COLO-357 Pancreatic Cancer Cells and Is Overexpressed in Pancreatic Cancer

https://doi.org/10.1006/bbrc.1999.0171Get rights and content

Abstract

Transforming growth factor (TGF)-β signaling is initiated by heterodimerization of TGF-β receptor type I (TβRI) and type II (TβRII). 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-β signaling. In the present study we demonstrate that Smad6 is overexpressedin vivoin human pancreatic cancer cells. We also show that stable transfection of a full-length Smad6 construct into COLO-357 pancreatic cancer cells abrogates TGF-β1 induced growth inhibition, and leads to enhanced anchorage-independent growth. Thus, enhanced expression of the TGF-β signaling inhibitor Smad6 in pancreatic cancer may present a novel mechanism of TGF-β resistance, which might have the potential to enhance the transformed phenotype of human cancer cells.

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      Citation Excerpt :

      The TGF-β–signaling inhibitors Smad6 and Smad7 are also markedly overexpressed in PDAC [60,61]. Transfection of the TGF-β–-responsive pancreatic cancer cell line COLO-357 with Smad6 and Smad7 resulted in abrogation of growth inhibition by TGF-β [60,61]. Recently, 2 research groups reported the establishment of Smad4 knockdown pancreatic cancer cell lines [68,69].

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    1

    Current address: Praecis Pharmaceuticals, Cambridge, MA 02139.

    2

    To whom correspondence should be addressed. Division of Endocrinology, Diabetes and Metabolism, Medical Sciences I, C240, University of California, Irvine, CA 92697. Fax: 949-824-1035. E-mail:[email protected].

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