Reversible activation of c-Myc in skin: Induction of a complex neoplastic phenotype by a single oncogenic lesion
Reversible activation of c-Myc in skin: Induction of a complex neoplastic phenotype by a single oncogenic lesion
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DOI：
10.1016/s1097-2765(00)80350-0
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发表时间：
1999-05-01
期刊：
影响因子：
16
通讯作者：
Evan, G
中科院分区：
文献类型：
--
作者：
Pelengaris, S;Littlewood, T;Evan, G
原癌基因c-myc调控细胞的生长、分化和凋亡，其异常表达常见于人类肿瘤中。然而，在成人组织中激活c-Myc的后果仍不清楚，在成人组织中，这些细胞过程是正常内稳态的一部分。为了实现这一点，我们有针对性地将c-Myc蛋白的一种可切换形式表达到皮肤表皮，这是一种具有良好特性的动态平衡组织。我们发现，c-Mycer(TM)在成人基底上皮中的激活迅速触发有丝分裂后角质形成细胞的增殖并破坏其分化。C-Myc的持续激活足以诱发乳头状瘤病和血管生成-类似于增生性光化性角化病，这是一种常见的人类癌前病变。所有这些癌前病变在c-MycER(TM)失活后自动消退。
The protooncogene c-myc regulates cell growth, differentiation, and apoptosis, and its aberrant expression is frequently observed in human cancer. However, the consequences of activating c-Myc in an adult tissue, in which these cellular processes are part of normal homeostasis, remain unknown. In order to achieve this, we have targeted expression of a switchable form of the c-Myc protein to the skin epidermis, a well characterized homeostatic tissue. We show that activation of c-MycER(TM) in adult suprabasal epidermis rapidly triggers proliferation and disrupts differentiation of postmitotic keratinocytes. Sustained activation of c-Myc is sufficient to induce papillomatosis together with angiogenesis-changes that resemble hyperplastic actinic keratosis, a commonly observed human precancerous epithelial lesion. All these premalignant changes spontaneously regress upon deactivation of c-MycER(TM).