Insulin-like growth factor binding protein-3 (IGFBP-3) sensitivity and signalling in breast cancer

体内所有组织的生长都依赖于许多生长因子、激素和其他蛋白质，它们共同作用来控制细胞分裂。这些因素中有些刺激组成身体组织的细胞分裂，有些则抑制细胞分裂，因此这些刺激因子和抑制因子的平衡确保组织不会长得太快或太大。乳腺癌的发展和乳腺肿瘤的生长被认为是由于调节乳腺细胞繁殖方式的蛋白质和激素的不受控制或错误的行为。正常情况下调节乳腺细胞分裂的一种蛋白质是IGFBP-3。我们发现，在一些乳腺癌细胞中，IGFBP-3不再能够抑制细胞分裂，这可能导致肿瘤生长和侵袭其他组织。我们感兴趣的是找出IGFBP-3通常是如何控制乳腺细胞增殖的，以及为什么一些乳腺癌对IGFBP-3有抗药性。为此，我们将使用培养的正常乳腺细胞来检查IGFBP-3如何与其他细胞因子相互作用以阻止细胞分裂。然后，我们将观察乳腺癌细胞是否发生了变化，使它们不再能够识别作为抑制蛋白的IGFBP-3。这可能是因为IGFBP-3与乳腺癌细胞结合的方式发生了变化，或者是因为它与细胞中其他蛋白质相互作用的方式发生了变化。因为IGFBP-3是由正常和乳腺癌细胞产生的，我们还将研究乳腺癌细胞产生的IGFBP-3是否正常，或者是否以某种方式改变使其失去活性。通过了解为什么有些乳腺癌不受IGFBP-3的抑制，我们将能够设计出新的更好的方法来预防、检测和治疗所有乳腺肿瘤的生长。

The growth of all tissues in the body depends on many growth factors, hormones and other proteins which work together to control cell division. Some of these factors stimulate the division of the cells which make up the body tissues, and some inhibit it, so that a balance of these stimulators and inhibitors ensures that tissues do not grow too fast, or too large. The development of breast cancer and the growth of breast tumours is thought to be due to uncontrolled or faulty actions of the proteins and hormones which regulate the way breast cells multiply. One protein which normally regulates the division of breast cells is IGFBP-3. We have found that in some breast cancer cells, IGFBP-3 is no longer able to inhibit cell division, and this may lead to tumour growth and invasion of other tissues. We are interested in finding out how IGFBP-3 normally controls breast cell proliferation, and why some breast cancers are resistant to IGFBP-3. To do this, we will use normal breast cells in culture to examine how IGFBP-3 interacts with other cellular factors to prevent cell division. We will then look at whether the breast cancer cells have changed so that they are no longer able to recognise IGFBP-3 as an inhibitory protein. This may be because of changes in the way IGFBP-3 binds to the breast cancer cell, or because of changes in the way it interacts with other proteins in the cell. Because IGFBP-3 is made by normal and breast cancer cells, we will also study whether the IGFBP-3 being made by breast cancer cells is normal, or if it changed in some way that makes it inactive. By understanding why some breast cancers are not inhibited by IGFBP-3, we will be able to design new and better methods of preventing, detecting and treating the growth of all breast tumours.