Interactions between IGFBP-3 and TGFbeta in the inhibition of breast cancer cell growth

IGFBP-3 和 TGFbeta 之间的相互作用抑制乳腺癌细胞生长

• 批准号: nhmrc : 211257
• 负责人: Dr Sue Firth
• 金额: $ 44.21万
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2002
• 资助国家: 澳大利亚
• 起止时间: 2002-01-01 至 2004-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/interactions-igfbp-3-cell-growth/96106
• 关键词: Interactions; between; IGFBP; TGFbeta; inhibition

A protein first identified by our research group, called insulin-like growth factor binding protein-3 or IGFBP-3, has been shown to be a potent inhibitor of the growth of cancer cells. High levels of IGFBP-3 in the bloodstream are associated with a decreased risk of several cancer types, including breast cancer. However, the way in which this protein prevents cancer cells from growing is poorly understood. This project will investigate an entirely novel idea, developed in our laboratory, that the actions of IGFBP-3 are intimately connected with the actions of another known cell growth inhibitor called transforming growth factor beta (TGFbeta). We have found that these two proteins initiate the same sequence of events leading to growth inhibition in breast cancer cells, and that a receptor protein required for TGFbeta activity is also needed for IGFBP-3 to be inhibitory. Our work has the potential to explain for the first time exactly how IGFBP-3 stops cancer cells from growing. This is important because it is an abundant protein in the body, and understanding how it acts may lead to the development of new approaches to cancer therapy that exploit our findings.

我们的研究小组首先发现了一种蛋白质，称为胰岛素样生长因子结合蛋白-3或IGFBP-3，已被证明是癌细胞生长的有效抑制剂。血液中高水平的IGFBP-3与几种癌症类型的风险降低有关，包括乳腺癌。然而，这种蛋白质阻止癌细胞生长的方式却知之甚少。该项目将研究我们实验室开发的一个全新的想法，即IGFBP-3的作用与另一种称为转化生长因子β（TGF β）的已知细胞生长抑制剂的作用密切相关。我们已经发现，这两种蛋白质启动导致乳腺癌细胞生长抑制的相同序列的事件，并且IGFBP-3也需要TGF β活性所需的受体蛋白来抑制。我们的工作有可能首次解释IGFBP-3如何阻止癌细胞生长。这很重要，因为它是体内丰富的蛋白质，了解它的作用方式可能会导致开发利用我们发现的癌症治疗新方法。