Ultraviolet-B irradiation alters the cell cycle machinery in murine epidermis in vivo
Ultraviolet-B irradiation alters the cell cycle machinery in murine epidermis in vivo
复制标题
DOI：
10.1046/j.0022-202x.2001.01536.x
复制
发表时间：
2001-11-01
影响因子：
6.5
通讯作者：
Fischer, SM
中科院分区：
文献类型：
--
作者：
Berton, TP;Pavone, A;Fischer, SM
小鼠皮肤的紫外线辐射会导致表皮增生、炎症以及随后的肿瘤发展。在这项研究中，我们确定了紫外线 B 辐射后表皮增殖过程中细胞周期机制的改变程度。最小红斑剂量（90 mJ/cm(2)）可使 G1 期细胞周期蛋白、细胞周期蛋白 DI 和 E 的蛋白表达增加 12 小时。通过 5'-溴-2'-脱氧尿苷掺入、增殖细胞核抗原和细胞周期蛋白 A 免疫组织化学测定，大多数表皮细胞在 18 至 24 小时之间进入 S 期。 12 小时后，细胞周期蛋白依赖性激酶 2 (cdk-2) 蛋白表达增加，但未观察到 cdk-4 或 cdk-6 蛋白水平发生变化。细胞周期蛋白 DI、E 和 A 蛋白表达的增加与细胞周期蛋白 D1-cdk-4、细胞周期蛋白 E-cdk-2 和细胞周期蛋白 A-cdk-2 复合物形成的增加相关。 p53蛋白表达在48小时内升高，cdk抑制蛋白p21(Cip1/WAF1)在12至24小时内升高6倍至7.5倍。在紫外线 B 照射后 3-24 小时和 6-24 小时，升高的 p21(Cip1/WAF1) 蛋白分别有助于增强与 cdk-2 和 cdk-4 的关联。这些数据表明，90 mJ/cm 2 的紫外线 B 照射通过增加 p53 和 p21(Cip1/WAF1) 蛋白表达来诱导 DNA 损伤反应，而且还诱导 S 期快速持续增加 18 小时。
Ultraviolet radiation of mouse skin leads to epidermal hyperplasia, inflammation, and subsequent tumor development. In this study we determined to what extent the cell cycle machinery is altered during epidermal proliferation after ultraviolet B radiation. A minimal erythema dose, 90 mJ per cm(2), increased the protein expression of the G1 phase cyclins, cyclin DI and E, by 12 h. The majority of epidermal cells entered S phase between 18 and 24 h as determined by 5'-bromo-2'-deoxyuridine incorporation, proliferating cell nuclear antigen, and cyclin A immunohistochemistry. An increase in cyclin-dependent kinase 2 (cdk-2) protein expression occurred after 12 h, but no changes in cdk-4 or cdk-6 protein levels were observed. The increase in cyclin DI, E, and A protein expression was associated with an increase in cyclin D1-cdk-4, cyclin E-cdk-2, and cyclin A-cdk-2 complex formation. p53 protein expression was elevated through 48 h, and the cdk inhibitor protein p21(Cip1/WAF1) was elevated 6-fold to 7.5-fold between 12 and 24 h. The elevated p21(Cip1/WAF1) protein contributed to an enhanced association with cdk-2 and cdk-4 at 3-24 h and 6-24 h post-ultraviolet B irradiation, respectively. These data indicate that 90 mJ per cm 2 of ultraviolet B irradiation induces a DNA damage response, by increasing p53 and p21(Cip1/WAF1) protein expression, but also induces a rapid and sustained increase in S phase by 18 h.