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

黑色素瘤易感性基因产物 p16 在紫外线诱导的人类皮肤细胞周期检查点中发挥作用

• 批准号: nhmrc : 102596
• 负责人: Prof Brian Gabrielli
• 金额: $ 13.61万
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2001
• 资助国家: 澳大利亚
• 起止时间: 2001-01-01 至 2002-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/melanoma-susceptibility-gene-human-skin/98041
• 关键词: Melanoma; Susceptibility; Gene; Product; p16

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.

阳光中的紫外线成分对皮肤癌的作用，特别是对黑色素瘤的作用，已被广泛承认。然而，紫外线辐射将正常皮肤黑素细胞（色素皮肤细胞）转变为恶性黑色素瘤的实际机制尚不清楚。几年前，一个基因被发现在高比例的散发性黑色素瘤中发生突变，并且在一部分具有发展黑色素瘤倾向的家庭中也发生突变。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不受控制，这是癌症的标志。本研究旨在探讨p16在正常皮肤细胞对紫外线辐射反应中的作用。我们将研究暴露于低剂量紫外线辐射后在皮肤中检测到的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的反应中的正常作用，也可能确定诊断，预防或治疗黑色素瘤的新靶点。