Transforming growth factor beta1 suppresses nonmetastatic colon cancer at an early stage of tumorigenesis.
Transforming growth factor beta1 suppresses nonmetastatic colon cancer at an early stage of tumorigenesis.
复制标题
DOI：
--
复制
发表时间：
1999-07
期刊：
影响因子：
11.2
通讯作者：
S. Engle;J. Hoying;G. Boivin;I. Ormsby;Peter S. Gartside;T. Doetschman
中科院分区：
文献类型：
--
作者：
S. Engle;J. Hoying;G. Boivin;I. Ormsby;Peter S. Gartside;T. Doetschman
已知转化生长因子β（TGF-β）途径在人类和尿液结肠癌中起重要作用。然而，分期，配体特异性，以及该途径的肿瘤抑制活性的机制尚不清楚。我们开发了一种结肠癌小鼠模型，确定了TGF-β 1在肿瘤抑制中的早期作用，并暗示TGF-β 2或TGF-β 3在预防转移中的作用。对TGF-β 1基因敲除小鼠结肠癌发展的分析将缺陷精确定位于增生/腺瘤过渡，并揭示该机制涉及无法维持上皮组织组织，而不是失去生长控制、炎症活动增加或遗传不稳定性增加。这些小鼠为研究TGF-β 1在结肠癌发展中的这一关键转变中的特定作用提供了独特的机会。
The transforming growth factor beta (TGF-beta) pathway is known to play an important role in both human and urine colon cancer. However, the staging, ligand specificity, and mechanism underlying the tumor suppressive activity of this pathway are unknown. We developed a mouse model for colon cancer that identifies an early role for TGF-beta1 in tumor suppression and implicates TGF-beta2 or TGF-beta3 in the prevention of metastasis. Analysis of the development of colon cancer in TGF-beta1 knockout mice pinpoints the defect to the hyperplasty/adenoma transition and reveals that the mechanism involves an inability to maintain epithelial tissue organization and not a loss of growth control, increased inflammatory activity, or increased genetic instability. These mice provide a unique opportunity to investigate the specific role of TGF-beta1 at this critical transition in the development of colon cancer.