Role of the Nuclear Growth Hormone Receptor in Cell Proliferation and Function

除了最终的身高，生长激素还调节体内的许多组织，并通过这些组织调节新陈代谢、身体成分、活力和衰老的各个方面。然而，有一些证据表明，生长激素也会促进癌症，特别是结肠癌和血细胞癌。我们在细胞核中发现了生长激素受体，特别是在许多癌症中，这使我们研究了核生长激素受体的作用。我们发现，将这种受体定位于细胞核允许细胞分裂，而不需要启动细胞分裂和生存的正常因素。我们还发现，生长激素受体的一部分起到了基因激活剂的作用，并鉴定了一些与受体结合的核蛋白，从而实现了这一点。这项提议旨在建立核生长激素受体和细胞分裂之间的联系，无论是从机制上还是在活动物中都是如此。我们还计划确定，人工定位受体的核是否会导致癌症的形成。这一结果将提供当前生长激素治疗的风险指数，并可能导致一种新的癌症治疗方法。

In addition to final height, growth hormone regulates many tissues in the body, and through these, regulates metabolism, body composition, vitality and aspects of ageing. However, there is some evidence that GH can also promote cancer, notably colon and blood cell cancers. Our discovery of the receptor for growth hormone in the cell nucleus, notably in many cancers, has led us to investigate the role of the nuclear GH receptor. We have found that targeting this receptor to the nucleus allows the cell to divide without the need for the normal factors which initiate cell division and survival. We have also found that a part of the GH receptor acts as a gene activator, and have identified some of the nuclear proteins which bind to the receptor and make this so. This proposal aims to establish the link between the nuclear GH receptor and cell division, both mechanistically, and in live animals. We also plan to establish if nuclear localizing the receptor artificially results in cancer formation. The outcome would provide an index of risk from current GH therapy, and could lead to a new cancer therapy.