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首页> 外文期刊>Oncogene >RAR|[gamma]| acts as a tumor suppressor in mouse keratinocytes
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RAR|[gamma]| acts as a tumor suppressor in mouse keratinocytes

机译：RAR |γ|在小鼠角质形成细胞中起肿瘤抑制作用

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All-trans retinoic acid (RA), the principle biologically active form of vitamin A, is essential for many developmental process as well as homeostasis in the adult. Many lines of evidence also suggest that RA, acting through the RA receptors (RARs), can also suppress growth of tumors of diverse origin. To assess directly the role of the RARs in a model of epidermal tumorigenesis, we investigated the incidence of tumor formation using keratinocytes lacking specific RAR types. Our data suggest that loss of RAR, but not RAR, predisposed keratinocytes to v-Ha-Ras-induced squamous cell carcinoma. We also found that ablation of RAR, but not RAR, abolished RA-induced cell cycle arrest and apoptosis in these keratinocytes. Reconstitution of receptor expression into RAR-null cells restored sensitivity to RA, and reversed the tumorigenic potential of receptor-deficient keratinocytes. These data strongly support a tumor suppressor effect for the RARs, in particular endogenous RAR, in murine keratinocytes.
机译：全反式维甲酸（RA）是维生素A的主要生物活性形式，对于成人的许多发育过程和体内平衡都是必不可少的。许多证据还表明，通过RA受体（RAR）起作用的RA也可以抑制多种来源的肿瘤的生长。为了直接评估RAR在表皮肿瘤发生模型中的作用，我们使用缺乏特定RAR类型的角质形成细胞调查了肿瘤形成的发生率。我们的数据表明，RAR的丧失（而非RAR的丧失）使角质形成细胞易患v-Ha-Ras诱导的鳞状细胞癌。我们还发现，RAR的消融（而不是RAR）消除了RA诱导的这些角质形成细胞的细胞周期停滞和凋亡。受体表达重建成RAR空细胞恢复了对RA的敏感性，并逆转了受体缺陷型角质形成细胞的致瘤潜力。这些数据强烈支持鼠角质形成细胞中RAR，特别是内源RAR的肿瘤抑制作用。

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