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TUMOR PROMOTING EFFECTS OF TGF-BETA1

TUMOR PROMOTING EFFECTS OF TGF-BETA1
TGF-BETA1 的促肿瘤作用
批准号:
6210159
负责人:
DEBABRATA SAHA
金额:
$3.92万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2000
资助国家:
美国
项目状态:
未结题
起止时间:
2000-11-01 至

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中文摘要
翻译
转化生长因子(tgf - β)是一种多功能因子,可诱导多种影响细胞生长和分化的过程。在包括肠上皮在内的正常上皮细胞中,tgf - β具有有效的生长抑制作用和肿瘤抑制作用。另一方面,在特定条件下,tgf - β实际上可能促进肿瘤发生。tgf - β受体和选择的tgf - β信号转导蛋白(Smad蛋白家族)的突变与很大一部分人类结直肠癌和胰腺癌有关。有证据表明,tgf - β的几种作用,如趋化活性和侵袭性增加,COX-2和前列腺素释放的表达增加以及RhoB表达的增加,导致COX-2和前列腺素释放的上皮到间质表达和RhoB表达的增加导致上皮到间质转化(EMT)。根据最近的观察,该提议的中心假设是:在肠道和其他类型的上皮细胞中,由于tgf - β信号转导的改变,tgf - β的促肿瘤作用超过了肿瘤抑制作用。这项研究的长期目标是确定新的治疗策略,选择性地靶向tgf - β的肿瘤促进作用,同时保留肿瘤抑制作用。
英文摘要
Transforming growth factor (TGF-beta) is a multi-functional factor that induces a wide variety of cellular processes affecting growth and differentiation. In normal epithelial cells, including intestinal epithelium, TGF-beta has a potent growth inhibitory effect and serves a tumor suppressor role. On the other hand, under selected conditions TGF-beta may actually promote tumorigenesis. Mutations in the TGF-beta receptors and selected TGF-beta signal transduction proteins (Smad family of proteins) have been associated with a significant fraction of human colorectal and pancreatic cancers. Evidence suggests that several effects of TGF-beta such as increased chemotactic activity and invasiveness, increased expression of COX-2 and prostaglandin release and increased expression of RhoB cause a epithelial to mesenchymal expression of COX-2 and prostaglandin release and increased expression of RhoB cause a epithelial to mesenchymal transition (EMT). Based on recent observations, the central hypothesis of this proposal is: tumor promoting effects of TGF-beta over-ride tumor suppressor effects during of intestinal and other types of epithelial cells, due to a witch in TGF-beta signal transduction. A long term of this investigation is to identify novel therapeutic strategies that selectively target the tumor promoting effects of TGF-beta, while preserving the tumor suppressive actions.
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Role of DAB2IP in Prostate Cancer Patients Treated with Radiation Therapy
  • 批准号:
    8637366
  • 项目类别:
  • 资助金额:
    $17.29万
  • 财政年份:
    2014
  • 负责人:
    DEBABRATA SAHA
  • 依托单位:
TUMOR PROMOTING EFFECTS OF TGF-BETA1
  • 批准号:
    6464047
  • 项目类别:
  • 资助金额:
    $4.38万
  • 财政年份:
    2001
  • 负责人:
    DEBABRATA SAHA
  • 依托单位:
海外基金