GENE TRAPPING TGF BETA TARGETS IN BREAST EPITHELIAL CELL

乳腺上皮细胞中基因捕获 TGF Beta 靶标

• 批准号: 6167531
• 负责人: ROBERT J LECHLEIDER
• 金额: $ 7.4万
• 依托单位: HENRY M. JACKSON FDN FOR THE ADV MIL/MED
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-01 至 2002-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6167531
• 关键词: carcinogenesis; cell growth regulation; cell line; gene induction /repression; genetic library; genetic transcription; mammary epithelium; transfection /expression vector; transforming growth factors

Transforming growth factor beta (TGF-beta) is a multifunctional cytokine that acts as a powerful anti-mitogen for normal epithelial cells. Growth inhibition by TGF-beta is often lost in transformed cells, which can then produce TGF-beta which acts as a local immunosuppressive and angiogenic factor. Thus, TGF-beta acts early as a tumor suppressor by maintaining a normal balance of cell growth, and later as a tumor promoter by increasing angiogenesis and suppressing host immune responses to transformed cells. Although much has been learned about how signals from TGF-beta cell surface receptors are transduced into changes in gene expression, little is known about the targets of TGF-beta signaling. Few of the genes likely to be up or down regulated by TGF-beta have been identified, and the critical targets necessary for regulation of growth by TGF-beta have not been fully defined. Our long term goal is to catalogue and identify the genes regulated by TGF-beta in normal breast epithelial cells, and to determine which of those genes is essential for maintenance of normal cellular homeostasis controlled by TGF-beta. Our hyposthesis is that transcriptional regulation of a few sets or classes of genes will be essential to mediating TGF-beta growth inhibitory effects, and that others will be essential for metastasis or other effects. We will use a gene trapping strategy in transformed, non-tumorigenic breast epithelial cells in order to identify those genes essential for TGF-beta regulation of growth and carcinogenesis.

转化生长因子 β (TGF-β) 是一种多功能细胞因子，可作为正常上皮细胞的强大抗有丝分裂原。 TGF-β 的生长抑制作用在转化细胞中通常消失，然后转化细胞可以产生 TGF-β，充当局部免疫抑制和血管生成因子。 因此，TGF-β早期通过维持细胞生长的正常平衡发挥肿瘤抑制因子的作用，随后通过增加血管生成和抑制宿主对转化细胞的免疫反应发挥肿瘤促进剂的作用。尽管人们对 TGF-β 细胞表面受体的信号如何转导为基因表达变化了解很多，但对 TGF-β 信号传导的靶标却知之甚少。 很少有可能被 TGF-β 上调或下调的基因已被识别，并且 TGF-β 调节生长所需的关键靶标尚未完全确定。我们的长期目标是编目和鉴定正常乳腺上皮细胞中受 TGF-β 调节的基因，并确定其中哪些基因对于维持 TGF-β 控制的正常细胞稳态至关重要。 我们的假设是，几组或几类基因的转录调节对于介导 TGF-β 生长抑制作用至关重要，而其他基因对于转移或其他作用则至关重要。 我们将在转化的非致瘤性乳腺上皮细胞中使用基因捕获策略，以确定那些对于 TGF-β 生长和癌变调节至关重要的基因。