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

我们的研究小组最先发现的一种蛋白质，称为胰岛素样生长因子结合蛋白-3或IGFBP-3，已被证明是一种有效的癌细胞生长抑制因子。血流中高水平的IGFBP-3与几种癌症类型的风险降低有关，包括乳腺癌。然而，这种蛋白质是如何阻止癌细胞生长的还知之甚少。这个项目将研究我们实验室开发的一个全新的想法，即IGFBP-3的作用与另一种已知的细胞生长抑制因子β转化生长因子(TGFbeta)的作用密切相关。我们发现，这两种蛋白质启动了相同的事件序列，导致乳腺癌细胞生长抑制，并且IGFBP-3也需要一种受体蛋白来抑制TGFbeta的活性。我们的工作有可能首次准确解释IGFBP-3是如何阻止癌细胞生长的。这一点很重要，因为它是体内一种丰富的蛋白质，了解它的作用方式可能会导致开发利用我们的发现的癌症治疗的新方法。

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.