权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

TUMOR PROMOTING EFFECTS OF TGF-BETA1

TGF-BETA1 的促肿瘤作用

基本信息

批准号：
6464047
负责人：
DEBABRATA SAHA
金额：
$ 4.38万
依托单位：
VANDERBILT UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2001
资助国家：
美国
起止时间：
2001-11-01 至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/6464047
关键词：
biological signal transduction carcinogenesis cell growth regulation cell line cell transformation epithelium gene expression gene mutation genetically modified animals guanine nucleotide binding protein laboratory mouse neoplastic process prostaglandin endoperoxide synthase protein protein interaction transforming growth factors

项目摘要

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.

转化生长因子是一种多功能因子，可诱导多种细胞过程影响生长和分化。在包括肠上皮在内的正常上皮细胞中，转化生长因子-β具有很强的生长抑制作用和肿瘤抑制作用。另一方面，在选定的条件下，转化生长因子-β实际上可能促进肿瘤的发生。转化生长因子-β受体和特定的转化生长因子-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，转化生长因子-β的多种作用，如增加趋化活性和侵袭力，增加COX-2的表达和前列腺素释放，以及增加RhoB的表达，导致上皮细胞向间充质细胞的表达，前列腺素释放和RhoB的增加，导致上皮细胞向间充质细胞的转变(EMT)。根据最近的观察，这一建议的中心假设是：由于转化生长因子-β信号转导的改变，在肠道和其他类型的上皮细胞中，转化生长因子-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，在保留肿瘤抑制作用的同时，选择性地针对转化生长因子-β的促肿瘤作用。