Drm/Gremlin transcriptionally activates p21Cip1 via a novel mechanism and inhibits neoplastic transformation
Drm/Gremlin transcriptionally activates p21Cip1 via a novel mechanism and inhibits neoplastic transformation
复制标题
DOI：
10.1016/s0006-291x(02)00828-8
复制
发表时间：
2002-08-02
影响因子：
3.1
通讯作者：
Blair, DG
中科院分区：
文献类型：
--
作者：
Chen, B;Athanasiou, M;Blair, DG
Drm/Gremlin是BMP拮抗剂Dan家族的成员，已知在早期胚胎发育中起作用，但在成人中也以组织特异性方式表达，并在转化细胞中显著下调。在这份报告中，我们证明了Drm在肿瘤衍生的细胞系Daoy（原始神经外胚层）和Saos-2（成骨细胞）中的过表达，无论是在蜕皮激素诱导型或组成型启动子下，都能显著抑制肿瘤发生。此外，Drm在这些细胞中的过表达增加了p21（Cip 1）蛋白的水平，并降低了磷酸化的p42/44 MAP激酶的水平。最后，我们的数据表明，Drm可以诱导P21（Cip 1）转录通过一种新的途径，是独立的p53和p38和p42/44 MAP激酶。这些结果提供了证据，Drm，可以作为一种新的转化抑制剂，并表明，这可能是通过其对p21（Cip 1）和磷酸化p42/44 MAPK的水平的影响。(C)2002 Elsevier Science（美国）。All rights reserved.
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.