CENP-50 is required for papilloma development in the two-stage skin carcinogenesis model.
CENP-50 is required for papilloma development in the two-stage skin carcinogenesis model.
复制标题
CENP-50 是两阶段皮肤癌模型中乳头状瘤发展所必需的。
DOI：
10.1111/cas.14533
复制
发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Wakabayashi Y.
中科院分区：
文献类型：
--
作者：
2.Saito M;Kagawa N;Okumura K;Munakata H;Isogai E;Fukagawa T;Wakabayashi Y.
CENP-50/U是CENP-0复合物（CENP-0/P/Q/R/U）的一种组分，在整个细胞周期中定位于着丝粒。CENP-50/U的异常表达已在许多类型的癌症中报道。然而，asCenp-50/U-缺陷小鼠在早期胚胎发生期间死亡，其功能在体内仍然知之甚少。为了研究Cenp-50/U在皮肤癌发生中的作用，我们产生了Cenp-50/U条件性敲除（K14 CreER-Cenp-50/Ufl/fl）小鼠，并使其接受7，12-二甲基苯并蒽（DMBA）/对苯二甲酸（TPA）化学致癌方案。结果，Cenp-50/U-缺陷小鼠的早期乳头状瘤减少。相比之下，Cenp-50/U-缺陷小鼠表现出与对照小鼠几乎相同的癌发生率。此外，使用DMBA/TPA诱导的乳头状瘤和癌的mRNA表达分析显示，乳头状瘤中的Cenp-50/U表达水平显著高于癌。这些结果表明，Cenp-50/U主要在乳头状瘤的早期发展中起作用，而对恶性转化几乎没有影响。
CENP‐50/U is a component of the CENP‐O complex (CENP‐O/P/Q/R/U) and localizes to the centromere throughout the cell cycle. Aberrant expression ofCENP‐50/Uhas been reported in many types of cancers. However, asCenp‐50/U‐deficient mice die during early embryogenesis, its functions remain poorly understood in vivo. To investigate the role ofCenp‐50/Uin skin carcinogenesis, we generatedCenp‐50/Uconditional knockout (K14CreER‐Cenp‐50/Ufl/fl) mice and subjected them to the 7,12‐dimethylbenz(a)anthracene (DMBA)/terephthalic acid (TPA) chemical carcinogenesis protocol. As a result, early‐stage papillomas decreased inCenp‐50/U‐deficient mice. In contrast,Cenp‐50/U‐deficient mice demonstrated almost the same carcinoma incidence as control mice. Furthermore, mRNA expression analysis using DMBA/TPA‐induced papillomas and carcinomas revealed thatCenp‐50/Uexpression levels in papillomas were significantly higher than in carcinomas. These results suggest thatCenp‐50/Ufunctions mainly in early papilloma development and it has little effect on malignant conversion.