The Melanoma Susceptibility Gene Product p16 Functions in a UV-induced Cell Cycle Checkpoint in Human Skin

一般来说，阳光中的紫外线成分对皮肤癌，尤其是黑色素瘤的作用是公认的。然而，紫外线辐射将正常的皮肤黑色素细胞，即色素皮肤细胞转变为癌变黑色素瘤的实际机制尚不清楚。几年前，一种基因被发现在很大比例的散发性黑色素瘤中发生突变，并且在一些易患黑色素瘤的家庭中也被发现发生突变。这种黑色素瘤易感基因p16可以阻止细胞生长，因此在疾病中失去这种基因功能可能导致细胞生长失控，这是癌症的一个标志。本研究旨在探讨p16在正常皮肤细胞对紫外线辐射的反应中的作用。我们将检查暴露于低剂量紫外线辐射后皮肤中检测到的p16水平的增加，并试图确定这些细胞对p16水平增加的生长反应。该项目将有助于确定p16在细胞对紫外线辐射反应中的正常作用，也可能确定诊断、预防或治疗黑色素瘤的新靶点。

The contribution of the ultraviolet component of sunlight to skin cancer generally, and melanoma in particular, is widely acknowledged. However, the actual mechanism by which ultraviolet radiation changes the normal skin melanocytes, the pigmented skin cells, into cancerous melanomas is unclear. Several years ago, a gene was identified that was found to be mutated in a high proportion of sporadic melanomas, and was also found to be mutated in a proportion of families with a predisposition to developing melanoma. This melanoma susceptibility gene, p16, can act to block cells growth, thus loss of this gene function in disease could lead to uncontrolled cell growth, a hallmark of cancer. This proposal investiagtes the role of p16 in responses of normal skin cells to ultraviolet radiation. We will examine the increased levels of p16 detected in skin after exposure to low doses of ultraviolet radiation and attempt to define the growth responses of these cells to the increased p16 levels. This project will help to establish the normal role of p16 in cellular responses to ultraviolet radiation, and may also identify novel targets for diagnosis, prevention or treatment of melanoma.