Department of Carcinogenesis Research, Division of Experimental Animal Research, Chiba Cancer Center Research Institute, Chiba, Japan.
Department of Molecular Genetics, National Institute of Genetics and The Graduate University for Advanced Studies, Mishima, Japan.
Cancer Sci. 2020 Aug;111(8):2850-2860. doi: 10.1111/cas.14533. Epub 2020 Jul 6.
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 of CENP-50/U has been reported in many types of cancers. However, as Cenp-50/U-deficient mice die during early embryogenesis, its functions remain poorly understood in vivo. To investigate the role of Cenp-50/U in skin carcinogenesis, we generated Cenp-50/U conditional knockout (K14Cre -Cenp-50/U ) 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 in Cenp-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 that Cenp-50/U expression levels in papillomas were significantly higher than in carcinomas. These results suggest that Cenp-50/U functions mainly in early papilloma development and it has little effect on malignant conversion.
CENP-50/U 是 CENP-O 复合物(CENP-O/P/Q/R/U)的一个组成部分,在整个细胞周期中定位于着丝粒。在许多类型的癌症中都报道了 CENP-50/U 的异常表达。然而,由于 Cenp-50/U 缺陷型小鼠在胚胎早期死亡,因此其在体内的功能仍知之甚少。为了研究 Cenp-50/U 在皮肤致癌中的作用,我们生成了 Cenp-50/U 条件性敲除(K14Cre-Cenp-50/U)小鼠,并对其进行了 7,12-二甲基苯并(a)蒽(DMBA)/对苯二甲酸(TPA)化学致癌作用方案。结果表明, Cenp-50/U 缺陷型小鼠的早期乳头瘤减少。相比之下,Cenp-50/U 缺陷型小鼠的癌发生率与对照组小鼠几乎相同。此外,使用 DMBA/TPA 诱导的乳头瘤和癌进行的 mRNA 表达分析表明,Cenp-50/U 在乳头瘤中的表达水平明显高于在癌中的表达水平。这些结果表明,Cenp-50/U 主要在早期乳头瘤的发展中起作用,对恶性转化几乎没有影响。