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Drm/Gremlin transcriptionally activates p21(Cip1) via a novel mechanism and inhibits neoplastic transformation

  1. Author:
    Chen, B.
    Athanasiou, M.
    Gu, Q. P.
    Blair, D. G.

  2. Author Address

    NCI, Frederick Canc Res & Dev Ctr, Basic Res Lab, Bldg 469,Rm 102, Frederick, MD 21702 USA NCI, Frederick Canc Res & Dev Ctr, Basic Res Lab, Frederick, MD 21702 USA NCI, SAIC Frederick Inc, Intramural Res Support Program, Frederick, MD 21702 USA Blair DG NCI, Frederick Canc Res & Dev Ctr, Basic Res Lab, Bldg 469,Rm 102, Frederick, MD 21702 USA
    1. Year: 2002
  2. Journal: Biochemical and Biophysical Research Communications
    1. 295
    2. 5
    3. Pages: 1135-1141
  4. Type of Article: Article
  1. Abstract:

    Drm/Gremlin, a member of the Dan family of BMP antagonists, is known to function in early embryonic development, but is also expressed in a tissue-specific fashion in adults and is significantly downregulated in transformed cells. In this report, we demonstrate that overexpression of Drm in the tumor- derived cell lines Daoy (primitive neuroectodermal) and Saos-2 (osteoblastic), either under ecdysone-inducible or constitutive promoters, significantly inhibits tumorigenesis. Furthermore, Drm overexpression in these cells increases the level of p21(Cip1) protein and reduces the level of phosphorylated p42/44 MAP kinase. Finally, our data indicate that Drm can induce P21(Cip1) transcriptionally via a novel pathway that is independent of p53 and the p38 and p42/44 MAP kinases. These results provide evidence that Drm, can function as a novel transformation suppressor and suggest that this may occur through its affect on the levels of p21(Cip1) and phosphorylated p42/44 MAPK. (C) 2002 Elsevier Science (USA). All rights reserved.

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