The relationship between overexpression of cyclin D1 and prognostic factors on pharyngeal cancer. (molecular biological approach)

细胞周期蛋白D1是细胞周期调控因子，对细胞周期的G1-S期进程起着至关重要的作用。该基因位于染色体11q13上，在许多肿瘤细胞中观察到异常扩增。它还与许多其他与细胞周期相关的蛋白如CDK4、增殖细胞核抗原等形成络合物，并形成一个周期素盒，调节细胞周期。在本研究中，我们用免疫组织化学和分子生物学方法分析了一系列人咽癌组织中细胞周期蛋白D1mRNA的扩增和蛋白的过度表达。结合患者的临床和病理特点进行分析，发现细胞周期蛋白D1和CDK4基因扩增之间存在很强的相关性，提示在肿瘤细胞周期中，这两种基因的扩增是在同一时期进行的。此外，我们还发现Cyclin D1蛋白在低分化癌和高分化癌中都有较强的过表达。提示该扩增子中的其他基因也可能参与癌变的进展和分化。此外，我们还分析了细胞周期蛋白D1的表达和CDK4的mRNA扩增与增殖细胞核抗原蛋白的过度表达存在相关性。这与细胞周期蛋白D1和CDK4的表达代表细胞调控在咽癌中的重要作用这一观点是一致的。

Cyclin D1 is a cell cycle regulator essential for G1-S phase progression. The gene is located on chromosome llq13, which the abnormal amplification has been observed in many tumor cells. It also complexes with many other cell cycle related proteins such as cdk4, PCNA, and makes a cyclin box, which regulates the cell cycle. In this study, we have analyzed cyclin D1 mRNA amplification and protein overexpression in a series of human pharyngeal carcinomas using immunohistochemical and molecular biological methods. The results were analyzed against the clinical and pathological characteristics of the patients.A strong correlation was observed between the cyclin D1 and cdk4 mRNA amplification, suggesting that these genes would be amplified in the same phase in the tumor cell cycles. Also, we found that strong overexpressions of the cyclin D1 protein were seen not only in the poorly differentiated carcinomas, but also in the well-differentiated carcinomas. It suggests that the other genes in this amplicon may also be involved in the progression and differentiation of carcinogenesis. Additionally, we analyzed that the expression of cyclin D1 and cdk4 mRNA amplification had a correlation with the overexpression of PCNA protein. This data are consistent with the notion that the expression of cyclin D1 and cdk4 represents an important role of the cell regulation in pharyngeal carcinomas.