Skin Carcinogenesis Studies Using Mouse Models with Altered Polyamines.
Skin Carcinogenesis Studies Using Mouse Models with Altered Polyamines.
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DOI：
10.4137/cgm.s21219
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Shantz LM
中科院分区：
文献类型：
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作者：
Nowotarski SL;Feith DJ;Shantz LM
非黑色素瘤皮肤癌(NMSC)是世界范围内的主要健康问题。随着器官移植受者和服用光敏药物的患者等高危群体人数的增加，NMSC的发病率继续上升。NMSC的小鼠模型使我们能够更好地了解参与皮肤肿瘤发展的分子信号级联，以确定新的治疗策略。在这里，我们回顾了为确定多胺在NMSC发育和维持中的作用而设计的模型。肿瘤生长绝对需要增加的多胺，在NMSC中观察到其生物合成和分解代谢酶的失调。使用表皮多胺基因改变的小鼠的研究表明，它们在促进肿瘤和上皮细胞生存途径中发挥关键作用，最近的临床试验表明，多胺代谢的药理抑制剂在NMSC的高危个体中显示出良好的前景。
Nonmelanoma skin cancer (NMSC) is a major health concern worldwide. With increasing numbers in high-risk groups such as organ transplant recipients and patients taking photosensitizing medications, the incidence of NMSC continues to rise. Mouse models of NMSC allow us to better understand the molecular signaling cascades involved in skin tumor development in order to identify novel therapeutic strategies. Here we review the models designed to determine the role of the polyamines in NMSC development and maintenance. Elevated polyamines are absolutely required for tumor growth, and dysregulation of their biosynthetic and catabolic enzymes has been observed in NMSC. Studies using mice with genetic alterations in epidermal polyamines suggest that they play key roles in tumor promotion and epithelial cell survival pathways, and recent clinical trials indicate that pharmacological inhibitors of polyamine metabolism show promise in individuals at high risk for NMSC.