喉鳞癌组织中CDK_4、cyclin D_1、P~(16)蛋白表达

目的：细胞周期中G1／S转换受到G1期的细胞周期蛋白及细胞周期蛋白的依赖激酶（CDKs）和它们的抑制剂的调节，cyclinD1／CDK4复合物磷酸化（pRB）基因产物、P16与cyclinD1竞争性地抑制CDK4，这些蛋白质的不正常表达就使细胞增殖失控，进而导致肿瘤的形成和发展。本研究从细胞周期调控的角度来探讨喉鳞状细胞癌的发生、发展与CDK4、cyclinD1及P16的关系。方法：用SP免疫组织化学的方法，检测了105例喉癌（其中声门上癌51例，声门癌54例）及28例声带息肉中CDK4、cyclinD1、P16蛋白表达的水平。结果显示：在喉癌组织中cyclinD1的表达以＋＋～＋＋＋为主，而在声带息肉组织中以阴性及弱阳性为主。它们之间存在着显著性的差异（P＜0．05）；而同样P16的表达在喉癌及对照组之间的差异非常显著（P＜0．001）。P16、CDK4的表达在声门上癌与声门癌之间差异显著，P值分别为P=0．002，P=0．021。经Spearman相关分析得出：喉癌组织中CDK4的表达与P16的表达和cyclinD1的表达具有相关性，相关系数分别为0．235、0．253。伴转移的喉癌组织中CDK4的表达与cyclinD1的表达相关明显，相关系数r=0．534。而在非转移的喉癌组织中CDK4与P16相关，相关系数r=0．253。由此我们推论：在喉癌的发生、发展中CDK4、cyclinD1及P16是共

The expression of CDK_4, Cyclin D_1, P~(16) proteins in 105 patients with laryngeal squamous cell carcinomas

G1/S transition of cell cycle is regulated by G1 cyclins/cyclin-dependentkinases (CDKs ) and their inhibitors. Cyclin D1/CDK4 complex phosphorylatesretinoblastoma (pRB) gene product and P16 inhibits CDK4 in competition with cyclin D1.Aberrant expression of these proteins may deregulate cell proliferation and moreovermay lead to tumor formation and progression. We postulated that increased expression ofthe cell cycle regulators cyclin D1 and cytlin-dependent kinase (CDK4) might be involvedin oncogenesis and development of laryngeal squamous cell carcinomas (LSCC).Results:Between the supraglottic cancer (SGC) (51 cases ) and the glottic cancer(GC) (54 cases) there were significant difference. The expressions of P16 and CDK4,their P values were 0. 002 and 0.021. The over-expression of cyclin D, was mainly on ++ ~ + + + in LSCC,whereas in polyp of vocal cord (28 cases ) was mainly on --~ +.They revealed significant difference in the same time (P <0. 05). It was the same results with the over-expression of P16(P<0.001). It showed strong correlation betweennuclear over-expression of CDK4 in cancer cells and the expression of P16 and cyclin D1 bySpearman Correlation Analysis. In lymphatic node metastatic cases,the coexpression of CDK4 and cyclin D1 was obviouslycorrelative and the relative coefficient wasr = 0. 534,whereas in no lymphatic node metastatic cases,CDK4 correlated with P16 andits coefficient was r= 0. 253. These results indicated that both cyclin D1 and CDK4 maycontribute to phosphorylation of PRB. P16 over-expression would be induced as a brake atG1/S transition through PRB phosphorylation by CDK4 over-expression in LSCC. In conclussion,the results suggested that inappopriate coexpression of Cyclin D1 .CDK4 and P16may react on the oncogenesis and development of LSCC.