Youssef E M, Hasuma T, Morishima Y, Takada N, Osugi H, Higashino M, Otani S, Fukushima S
First Department of Pathology, Osaka City University Medical School, Abeno-ku.
Jpn J Cancer Res. 1997 Jan;88(1):18-25. doi: 10.1111/j.1349-7006.1997.tb00296.x.
Overexpression of cyclin D1 in human esophageal carcinomas has been well documented. The aim of the present study was to assess the expression of cyclin D1 in different types of esophageal epithelial lesions induced by N-nitrosomethylbenzylamine (NMBA) in rats. A total of 30 rats received s.c.-injections, five times/week, of 1.0 mg/kg NMBA for a period of 5 weeks followed by the same dose once per week for another 10 weeks. An additional 15 rats were given saline and used as controls to provide normal epithelium. The tumor incidence was 100% at the termination point of 21 weeks. Seventeen rats (57%) showed nuclear staining for cyclin D1, with a great variation in the intensity, as demonstrated by using an immunohistochemical technique. The cyclin D1 positive indices were in the range of 0% to 60% of the individual cells. Negligible staining was observed for normal esophageal epithelium, with a minimal increase in hyperplastic and dysplastic lesions. A significant elevation of cyclin D1 levels was observed in tumors. However, no significant differences were found between papillomas and carcinomas. The immunohistochemical results were confirmed by western blotting analysis. Tumors, papillomas and carcinomas overexpressing cyclin D1 had elevated proliferating cell nuclear antigen (PCNA) indices (P < 0.05). The correlation coefficient of overexpressions of PCNA and cyclin D1 was r = 0.7 for papillomas, but only r=0.3 for carcinomas. The study thus provides strong evidence of relatively early overexpression of cyclin D1 during tumorigenesis in the present rat esophageal model. Cyclin D1 expression is not simply a direct consequence of increase cell proliferation.
细胞周期蛋白D1在人食管癌中的过表达已有充分记载。本研究的目的是评估细胞周期蛋白D1在N-亚硝基甲基苄胺（NMBA）诱导的大鼠不同类型食管上皮病变中的表达。总共30只大鼠接受皮下注射，每周5次，每次1.0mg/kg NMBA，持续5周，随后每周一次相同剂量，再持续10周。另外15只大鼠给予生理盐水作为对照，以提供正常上皮。在21周的终点时肿瘤发生率为100%。17只大鼠（57%）显示细胞周期蛋白D1的核染色，强度差异很大，采用免疫组织化学技术证实。细胞周期蛋白D1阳性指数在单个细胞的0%至60%范围内。正常食管上皮观察到可忽略不计的染色，增生性和发育异常性病变仅有轻微增加。在肿瘤中观察到细胞周期蛋白D1水平显著升高。然而，乳头状瘤和癌之间未发现显著差异。免疫组织化学结果通过蛋白质印迹分析得到证实。过表达细胞周期蛋白D1的肿瘤、乳头状瘤和癌的增殖细胞核抗原（PCNA）指数升高（P<0.05）。PCNA和细胞周期蛋白D1过表达的相关系数，乳头状瘤为r = 0.7，但癌仅为r = 0.3。因此，本研究为在当前大鼠食管模型中肿瘤发生过程中细胞周期蛋白D1相对早期的过表达提供了有力证据。细胞周期蛋白D1的表达不仅仅是细胞增殖增加的直接结果。
