The role of the EphA1 in the normal epithelial organs and in epithelial tumour progression.

最初发现Eph蛋白家族在正常发育过程中起着重要作用。在人类中，这与怀孕的前12周相对应。在这些研究的同时，其他工作提供了证据，证明这些蛋白质在一些人类癌症中异常高水平。最近的证据表明，这些蛋白质在维持正常组织和非恶性疾病中发挥着重要作用。该提案试图了解其中一种蛋白质(EPHA1)是如何在形成皮肤、肝脏、肾脏、乳房和前列腺的细胞中发挥作用的。这些细胞还构成口腔、胃、肠和肺的内层。了解EPHA1蛋白和这个家族的其他成员如何合作控制这些器官的发育和维护，将使我们能够确定该蛋白是否可能与这些器官的先天性缺陷和疾病(如肾衰竭、肝硬变和皮肤病)有关。该项目的第二个主要目标是进一步探索Eph蛋白在广泛的人类癌症中异常高表达的观察结果。这种异常表达与肿瘤在全身扩散直接相关。EPHA1在肠癌、肺癌、乳腺癌和前列腺癌中异常高表达。这些是人类最常见的癌症，也是最难治疗的癌症之一。这项拟议的工作询问EPHA1如何促进这些癌症的发展和进展。这些结果将对开发针对EPHA1蛋白的治疗具有非常直接的影响。

The Eph family of proteins were initially found to be important in normal development. In humans this corresponds to the first 12 weeks of pregnancy. In parallel with these studies, other work provided evidence of abnormally high levels of these proteins in a number of human cancers. More recent evidence suggests that these proteins have important roles in the maintenance of normal tissues and in non-malignant diseases. This proposal seeks to understand how one of these proteins (EphA1) works in the cells which form the skin, liver, kidneys, breast and prostate. These cells also form the lining of the mouth, stomach, bowel and lungs. Understanding how the EphA1 protein and other members of this family cooperate to control the development and maintenance of these organs will allow us to determine whether this protein might be involved in congenital defects and diseases in these organs (such as kidney failure, cirrhosis of the liver and skin diseases). A second main aim of this project is to explore further the observation that Eph proteins are abnormally highly expressed in a wide rangre of human cancers. This abnormal expression is directly correlated with the tumours spreading throughout the body. EphA1 is abnormally highly expressed in cancers of the bowel, lung, breast and prostate. These are the commonest cancers in man and some of the most difficult to treat. The work proposed asks how EphA1 contributes to the development and progression of these cancers. These results will have very direct implications for the development of therapies which target the EphA1 protein.