大肠癌胃泌素、生长抑素的表达及比势与细胞周期调控基因的相关性

目的:探讨大肠癌组织中胃泌素(GAS)、生长抑素(SS)的表达及其比势与细胞周期调控蛋白P16~(INK4a)、P21~(CIP1)及细胞周期素(Cyclins)、细胞周期依赖性蛋白激酶(CDKs)表达的关系.方法:随机选择79例大肠癌患者的手术切除标本,采用免疫组化SP法检测GAS、SS、P16~(INK4a)、P21~(CIP1)、Cvclin D1、Cvclin E、Cyclin A、Cyclin B1、CDK2、CDK4的表达情况.结果:Cyclin D1、CDK2、CDK4、Cyclin A在GAS高表达组、中表达组的阳性表达率明显高于低表达组;而P16~(INK4a)、P21~(CIP1)阳性表达率与此相反.cyclin E在SS低表达组的阳性表达率明显高于中表达组、高表达组;P21~(CIP1)在ss高表达组、中表达组的阳性表达率明显高于低表达组;CDK2在SS低表达组的阳性表达率明显高于SS高表达组.大肠癌组织中GAS、SS表达的积分比值(GAS/SS)与Cyclin D1(r =0.252)、Cyclin E(r=0.387)、Cyclin A(r= 0.466)、CDK2(r=0.519)、CDK4(r=0.434)呈正相关(P<0.01)与P16~(INK4a)(r=-0.385)、P21~(CIP1)(r =-0.454)蛋白的表达积分呈负相关(P<0.01).结论:GAS、SS对大肠癌细胞生长的调控可能与P16~(INK4a)、P21~(CIP1)、Cvclin D1、Cvclin A、CDK2、CDK4、cvclin E基因异常表达有关.GAS对大肠癌细胞周期的调控位点可能在G1、S、G2期,SS对大肠癌细胞周期的调控位点可能在G1/S、G2/M期的交界点,即S、M期的入口.对大肠癌GAS/SS积分比值分析、可作为临床大肠癌生物学行为的重要评估指标.

Correlations among gastrin and somatostatin expressions and the cell cycle: controlling genes in large intestine carcinomas

AIM:To explore correlations among the expression of gastrin (GAS),somatostatin (SS), P16~(INK4a),P21~(CIP1),Cyclins,and Cyclin-dependent- kinases (CDKs) in large intestine carcinomas. METHODS:Seventy-nine resected large intestine carcinomatous specimens were randomly select- ed.GAS,SS,p16~(INK4a),p21~(CIP1),Cyclin D1,Cyclin E, Cyclin A,Cyclin B1,CDK2,and CDK4 were de- tected by immunohistochemistry (Streptavidin- Peroxidase,SP). RESULTS:Positive expression rates of Cyclin D1,CDK2,CDK4,and Cyclin A were signifi- cantly higher in cases showing high or medium expression levels of GAS than in cases with low GAS expression.The positive expression rates of P16~(1NK4a) and P21~(CIP1) were the reverse.The posi- tive expression rate of Cyclin E was significantly lower in the high and middle SS expression groups than in the low SS expression group.The positive expression rate of P21~(CIP1) was signifi- cantly higher,and that of CDK2 was significant- ly lower,in the high and middle SS expression groups compared with the low SS expression group.The integral GAS/SS was positively cor- related with Cyclin D1 (r=0.252),Cyclin E (r =0.387),Cyclin A (r=0.466),CDK2 (r=0.519), and CDK4 (r=0.434,P<0.01),but negatively correlated with P16~(INK4a)(r=-0.385) and P21~(CIP1)(r =-0.454,P<0.01). CONCLUSION:The regulation and control of GAS and SS in large intestine carcinoma cell growth may be directly related to the abnormal expression of p16I~(NK4a),p21~(CIP1),Cyclin D1,Cy- clin A,CDK2 CDK4,and Cyclin E.The integral GAS/SS may be considered an important evalu- ating target for clinical determinations of the biological behavior of large intestine carcinomas.