Increased skin carcinogenesis in a keratinocyte directed thioredoxin-1 transgenic mouse.
Increased skin carcinogenesis in a keratinocyte directed thioredoxin-1 transgenic mouse.
复制标题
角化细胞定向硫氧还蛋白-1 转基因小鼠皮肤癌发生增加。
DOI：
10.1093/carcin/bgh195
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发表时间：
2004
期刊：
影响因子：
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通讯作者：
Powis,Garth
中科院分区：
文献类型：
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作者：
Mustacich,Debbie;Wagner,Amary;Williams,Ryan;Bair,Warner;Barbercheck,Loretta;Stratton,StevenP;Bhattacharyya,AchyutK;Powis,Garth
Thioredoxin-1 是一种低分子量氧化还原蛋白，可保护细胞免受氧化损伤。受阳光损伤的人体皮肤表皮层中的硫氧还蛋白-1 水平会升高。 Thioredoxin-1 水平在几种人类原发性肿瘤中也有所增加，其表达与肿瘤细胞增殖增加、细胞凋亡减少和侵袭性肿瘤生长相关。我们使用转基因小鼠研究了皮肤中硫氧还蛋白-1水平的增加是否会导致肿瘤形成增加，其中小鼠硫氧还蛋白-1在角质形成细胞中表达，受角质形成细胞-14 (K14)启动子的控制。转基因小鼠角质形成细胞层中的硫氧还蛋白-1 蛋白表达增加了 2 倍。皮肤宏观和组织学正常，但在使用局部二甲基苯并蒽（DMBA）作为引发剂和12-O-十四烷酰佛波醇-13-乙酸酯（TPA）作为促进剂的两阶段致癌模型中，与K14硫氧还蛋白-1转基因小鼠相比，每只小鼠的乳头状瘤数量增加了6倍，乳头状瘤大小增加了3倍与非转基因同窝仔猪。因此，在小鼠皮肤癌变的 DMBA/TPA 两阶段模型中，角质形成细胞中硫氧还蛋白-1 的增加可作为癌变增强剂。
Thioredoxin-1 is a low molecular weight redox protein that protects cells against oxidant damage. Thioredoxin-1 levels are increased in the epidermal layer of sun-damaged human skin. Thioredoxin-1 levels are also increased in several human primary tumors where its expression is associated with increased tumor cell proliferation, decreased apoptosis and aggressive tumor growth. We have investigated whether increased thioredoxin-1 levels in skin can lead to increased tumor formation using transgenic mice with mouse thioredoxin-1 expressed in keratinocytes under the control of the keratinocyte-14 (K14) promoter. Thioredoxin-1 protein expression was increased 2-fold in the keratinocyte layer of the transgenic mice. The skin was macroscopically and histologically normal but in the two-stage model of carcinogenesis using topical dimethylbenzanthracene (DMBA) as an initiator and 12-O-tetradecanoylphorbol-13-acetate (TPA) as a promoting agent, there was a 6-fold increase in the number of papillomas per mouse and a 3-fold increase in papilloma size in the K14 thioredoxin-1 transgenic mice compared with non-transgenic littermates. Thus, increased thioredoxin-1 in keratinocytes acts as an enhancer of carcinogenesis in the DMBA/TPA two-stage model of skin carcinogenesis in mice.