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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Suppressor role of activating transcription factor 2 (ATF2) in skin cancer
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Suppressor role of activating transcription factor 2 (ATF2) in skin cancer

机译：活化转录因子2（ATF2）在皮肤癌中的抑制作用

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Activating transcription factor 2 (ATF2) regulates transcription in response to stress and growth factor stimuli. Here, we use a mouse model in which ATF2 was selectively deleted in keratinocytes. Crossing the conditionally expressed ATF2 mutant with K14-Cre mice (K14.ATF2~(f/f)) resulted in selective expression of mutant ATF2 within the basal layer of the epidermis. When subjected to a two-stage skin carcinogenesis protocol [7,12-dimethylbenz[a]an-thracene/phorbol 12-tetradecanoate 13-acetate (DMBA/TPA)], K14.ATF2~(f/f) mice showed significant increases in both the incidence and prevalence of papilloma development compared with the WT ATF2 mice. Consistent with these findings, keratinocytes of K14.ATF2~(f/f) mice exhibit greater anchorage-independent growth compared with ATF2 WT keratinocytes. Papillomas of K14.ATF2~(f/f) mice exhibit reduced expression of presenilin1, which is associated with enhanced β-catenin and cyclin D1, and reduced Notch1 expression. Significantly, a reduction of nuclear ATF2 and increased β-catenin expression were seen in samples of squamous and basal cell carcinoma, as opposed to normal skin. Our data reveal that loss of ATF2 transcriptional activity serves to promote skin tumor formation, thereby indicating a suppressor activity of ATF2 in skin tumor formation.
机译：激活转录因子2（ATF2）调节转录，以响应压力和生长因子的刺激。在这里，我们使用在角质形成细胞中选择性删除ATF2的小鼠模型。将条件表达的ATF2突变体与K14-Cre小鼠（K14.ATF2〜（f / f））杂交，导致突变体ATF2在表皮基底层中选择性表达。经历两阶段皮肤致癌实验[7,12-二甲基苯并[a]-蒽/佛波醇12-十四烷酸酯13-乙酸酯（DMBA / TPA）]时，K14.ATF2〜（f / f）小鼠表现出显着增加与WT ATF2小鼠相比，乳头状瘤发展的发生率和患病率都更高。与这些发现一致的是，与ATF2 WT角质形成细胞相比，K14.ATF2〜（f / f）小鼠的角质形成细胞表现出更大的锚定非依赖性生长。 K14.ATF2〜（f / f）小鼠的乳头状瘤显示presenilin1的表达减少，这与增强的β-catenin和cyclin D1相关，并且Notch1的表达减少。明显地，与正常皮肤相反，在鳞状和基底细胞癌的样品中观察到核ATF2的减少和β-连环蛋白表达的增加。我们的数据表明，ATF2转录活性的丧失可促进皮肤肿瘤的形成，从而表明ATF2在皮肤肿瘤形成中具有抑制活性。

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