晒伤和p53在皮肤癌的发作中的作用
A Ziegler1, A S Jonason, D J Leffell
1Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut 06510.
Nature
|December 22, 1994
概括
阳光在皮肤癌的早期发育过程中导致p53瘤抑制基因突变 (行为性角质炎). 这会损害皮肤的皮肤.
科学领域:
- 在瘤学瘤学.
- 皮肤病学 皮肤病学
- 分子生物学分子生物学
背景情况:
- 状细胞癌 (SCC) 通过阶段进展,从阳光损伤的皮肤和行动性角质瘤 (AK) 开始.
- 来自阳光的紫外线 (UV) 辐射是已知的致癌物,但p53瘤抑制基因突变的确切阶段尚不清楚.
- 皮肤对DNA损伤的反应中p53的作用需要进一步阐明.
研究的目的:
- 为了确定皮肤癌发育的哪个阶段,阳光会诱导p53突变.
- 为了确定p53基因在皮肤对紫外线辐射的反应中的功能.
- 了解p53突变如何促进皮肤瘤的启动和促进.
主要方法:
- 在人类皮肤病变 (表皮,AK,SCC) 中对p53突变的分析.
- 在小鼠皮肤中,p53基因的失活.
- 在野外类型和p53缺乏的小鼠中,评估紫外线暴露后的角质细胞亡和晒伤细胞的形成.
主要成果:
- 在SCC中常见的p53突变在行动性角质炎病变中被发现.
- 在小鼠中非活化p53减少了紫外线诱导的角质细胞亡 (晒伤细胞).
- 这表明p53依赖的"组织守护者"机制可以消除癌前细胞.
结论:
- 太阳光通过突变p53基因,同时起到皮肤癌的启动和促进作用.
- 皮肤细胞中的p53突变损害了DNA损伤反应,允许受损细胞存活和繁殖.
- 这导致p53-突变细胞的克隆扩张,形成动因性角质炎,并向SCC进展.
相关概念视频
Mutations
Overview
Abnormal Proliferation
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
Mutations
Mutations are changes in the sequence of DNA. These changes can occur spontaneously or they can be induced by exposure to environmental factors. Mutations can be characterized in a number of different ways: whether and how they alter the amino acid sequence of the protein, whether they occur over a small or large area of DNA, and whether they occur in somatic cells or germline cells.
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
Chromosomal Alterations Are Large-Scale Mutations
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Nucleotide Excision Repair
DNA Distortion and Damage
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The color of the skin is influenced by a number of pigments, including melanin, carotene, and hemoglobin. Recall that melanin is produced by cells called melanocytes, which are found scattered throughout the stratum basale of the epidermis. The melanin is transferred to the keratinocytes via melanosomes.
Melanin occurs in two primary forms: eumelanin that provides black and brown pigment and pheomelanin that provides red color. Dark-skinned individuals produce more melanin than those with pale...
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Skin cancer is a type of cancer that occurs when there is an abnormal growth of skin cells, usually triggered by damage to the DNA within the skin cells. It is primarily caused by exposure to ultraviolet (UV) radiation from the sun or artificial sources like tanning beds. Skin cancer is the most common type of cancer worldwide, and its incidence continues to rise.
Basal Cell Carcinoma (BCC): BCC is the most common type of skin cancer, accounting for about 80% of cases. It typically develops in...
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