Wang Q S, Sabourin C L, Wang H, Stoner G D
Division of Environmental Health Sciences, School of Public Health, Ohio State University, Columbus, OH, USA.
Carcinogenesis. 1996 Aug;17(8):1583-8. doi: 10.1093/carcin/17.8.1583.
Dysregulation of G1 cyclins has been implicated in several human malignancies. To further investigate the role of G1 cyclins in chemical carcinogenesis, the expression of cyclin D1 and cyclin E was analyzed by RT-PCR and immunohistochemical studies in N-nitrosomethylbenzylamine (NMBA)-induced rat esophageal tumorigenesis. Cyclin D1 mRNA levels were increased 2.8-fold in 25 week (P < 0.05) and 6.8-fold in 45 week (P < 0.01) papillomas induced by NMBA, when compared with normal rat esophageal epithelium. Cyclin E mRNA levels were increased 6.2-fold in 25 week (P < 0.01) and 6.9-fold in 45 week (P < 0.01) papillomas. Immunohistochemical staining revealed exclusive nuclear staining of both cyclin D1 and cyclin E. Furthermore, there was a sequential increase in cyclin D1- and cyclin E-positive cells from normal epithelium, to preneoplastic lesions, to papillomas. These findings suggest that overexpression of cyclin D1 and cyclin E occur relatively early in rat esophageal tumorigenesis and participate in tumor progression in this model.
G1 细胞周期蛋白的失调与多种人类恶性肿瘤有关。为了进一步研究 G1 细胞周期蛋白在化学致癌过程中的作用，通过逆转录聚合酶链反应（RT-PCR）和免疫组织化学研究，分析了 N-亚硝基甲基苄胺（NMBA）诱导的大鼠食管肿瘤发生过程中细胞周期蛋白 D1 和细胞周期蛋白 E 的表达情况。与正常大鼠食管上皮相比，NMBA 诱导的 25 周龄乳头状瘤中细胞周期蛋白 D1 的 mRNA 水平增加了 2.8 倍（P < 0.05），45 周龄乳头状瘤中增加了 6.8 倍（P < 0.01）。细胞周期蛋白 E 的 mRNA 水平在 25 周龄乳头状瘤中增加了 6.2 倍（P < 0.01），在 45 周龄乳头状瘤中增加了 6.9 倍（P < 0.01）。免疫组织化学染色显示细胞周期蛋白 D1 和细胞周期蛋白 E 均为细胞核染色。此外，从正常上皮到癌前病变再到乳头状瘤，细胞周期蛋白 D1 和细胞周期蛋白 E 阳性细胞呈逐渐增加趋势。这些发现表明，细胞周期蛋白 D1 和细胞周期蛋白 E 的过表达在大鼠食管肿瘤发生过程中相对较早出现，并参与了该模型中的肿瘤进展。
