Autophagy and GG-NER in UVB-induced skin cancer - Admin Supplement

摘要 拟议中的补充剂的主要目标是确定饮食的机制 补充维生素E衍生物可以预防UVB诱发的皮肤癌，这种皮肤癌是在 父拨款的范围。皮肤癌是美国最常见的癌症，其发病率持续上升 以惊人的速度。一个主要的危险因素是阳光中的紫外线辐射，导致DNA损伤和随后的 致癌突变。这些UVB诱导的整个基因组的DNA损伤产物由 全球基因组NER(GG-NER)机制。功能性GG-NER对于防止突变和皮肤是必不可少的 肿瘤发生学。预防皮肤癌的潜在有效策略之一是增强GG-NER 通过饮食补充维生素E的衍生品。然而，它的作用机制仍然很差。 明白了。最近，我们发现了维生素E衍生物在增强GG-NER方面的新作用。指导原则 我们的初步数据，我们假设这种膳食补充剂增强GG-NER，从而抑制UVB- 诱发皮肤癌。我们的假设将在两个具体目标上得到检验。目标1将决定机制 维生素E的衍生物通过它来调节GG-NER。目标2将确定维生素 E衍生物对UVB诱导的小鼠皮肤肿瘤形成的影响。成功完成我们提议的项目 将极大地扩展我们对维生素E衍生物在GG-NER和皮肤中的作用机制的了解 癌症，并可能为制定更好的皮肤癌预防和治疗策略提供新的机会 使用膳食补充剂维生素E衍生物。由于GG-NER对皮肤中的肿瘤抑制至关重要， 肺和脑18，我们在这里的工作在GG-NER调节维生素E衍生物可能不仅意义重大 对于皮肤癌，但也可能适用于其他类型的肿瘤。

Abstract The primary goal of the proposed supplement is to determine the mechanism by which dietary supplementation with a vitamin E derivative protects against UVB-induced skin cancer, which is within the scope of the parent grant. The incidence of skin cancer, the most common cancer in the US, continues to rise at an alarming rate. One major risk factor is UVB radiation in sunlight, causing DNA damage and subsequent tumorigenic mutations. These UVB-induced DNA damage products across the genome are repaired by the global genome NER (GG-NER) machinery. Functional GG-NER is essential for preventing mutations and skin tumorigenesis. One of the potential effective strategies for preventing skin cancer is enhancing GG-NER through dietary supplementation with a vitamin E derivative. However, its mechanism of action remains poorly understood. Recently, we discovered a novel role for vitamin E derivative in enhancing GG-NER. Guided by our preliminary data, we hypothesize that this dietary supplement enhances GG-NER and thus inhibits UVB- induced skin cancer. Our hypothesis will be tested in two Specific Aims. Aim 1 will determine the mechanism by which the vitamin E derivative regulates GG-NER. Aim 2 will determine the mechanism by which the vitamin E derivative affects UVB-induced skin tumorigenesis in mice. Successful completion of our proposed project will vastly expand our knowledge of the mechanism of action of the vitamin E derivative in GG-NER and skin cancer, and may provide new opportunities for developing better strategies to prevent and treat skin cancer using dietary supplement vitamin E derivative. Since GG-NER is critical for tumor suppression in the skin, lungs, and brain 18, our work here in GG-NER regulation by the vitamin E derivative may not only be significant for skin cancer, but may also be applicable to other tumor types as well.