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

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，人们对这种蛋白质阻止癌细胞生长的方式知之甚少。这个项目将研究一个全新的想法，在我们的实验室发展，IGFBP-3的作用与另一种已知的细胞生长抑制剂称为转化生长因子β (tgfβ)的作用密切相关。我们发现这两种蛋白启动了导致乳腺癌细胞生长抑制的相同事件序列，并且TGFbeta活性所需的受体蛋白也需要IGFBP-3具有抑制作用。我们的工作有可能首次准确地解释IGFBP-3是如何阻止癌细胞生长的。这一点很重要，因为它在体内是一种丰富的蛋白质，了解它的作用方式可能会导致利用我们的发现开发新的癌症治疗方法。

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.