细胞周期调控系统相关因子Cyclin D1-CDK4-p21在瘢痕癌中的表达及意义
本文选题:瘢痕癌 + 细胞周期调控 ; 参考:《医学研究生学报》2014年09期
【摘要】:目的细胞周期调控机制失调是细胞增生肿瘤发生的重要因素。文中探讨细胞周期调控系统相关因子Cyclin D1-CDK4-p21在瘢痕癌中的表达及意义。方法选取遵义医学院病理教研室和中山大学附属第五医院病理科2005-2011年石蜡包埋标本,分为瘢痕癌组、病理性瘢痕组和正常皮肤组。应用组织化学法,分别检测瘢痕癌、病理性瘢痕和正常皮肤组织中Cyclin D1、CDK4、p21蛋白的表达。采用核酸分子原位杂交技术检测Cyclin D1 mRNA、CDK4 mRNA、p21 mRNA在3组组织中的表达。对各项指标进行相关性分析,计算平均光密度(表达强度)和阳性面积(表达水平)。结果 1Cyclin D1、CDK4、p21蛋白和Cyclin D1 mRNA、CDK4 mRNA、p21 mRNA在瘢痕癌癌组织呈强阳性表达,在病理性瘢痕上皮中呈弱阳性表达,在正常皮肤表皮呈弱阳性或阴性表达。瘢痕癌组CDK4蛋白表达强度(0.273±0.024)及表达水平(0.159±0.036)较正常皮肤组(0.194±0.013、0.053±0.086)、病理性瘢痕组(0.214±0.026、0.061±0.014)升高,瘢痕癌组CDK4 mRNA表达强度(0.281±0.033)、表达水平(0.207±0.039)较正常皮肤组(0.195±0.012、0.067±0.027)、病理性瘢痕组(0.235±0.021、0.080±0.032)高,差异有统计学意义(P0.01);瘢痕癌组Cyclin D1蛋白表达强度(0.262±0.023)、表达水平(0.141±0.036)较正常皮肤组(0.169±0.012、0.039±0.095)及病理性瘢痕组(0.176±0.039、0.065±0.013)高,瘢痕癌组Cyclin D1mRNA表达强度(0.264±0.031)、表达水平(0.201±0.041)较正常皮肤组(0.179±0.022、0.049±0.083)及病理性瘢痕组(0.193±0.021、0.068±0.035)高,差异均有统计学意义(P0.01);瘢痕癌组p21蛋白表达强度(0.148±0.031)、表达水平(0.275±0.032)较正常皮肤组(0.052±0.020、0.197±0.036)及病理性瘢痕组(0.062±0.021、0.214±0.032)高;瘢痕癌组p21 mRNA表达强度(0.227±0.059)较正常皮肤组(0.072±0.044、0.203±0.024)、病理性瘢痕组(0.075±0.041、0.223±0.021)高,差异均有统计学意义(P0.01);但病理性瘢痕组与正常皮肤组各项指标比较,差异无统计学意义(P0.05)。2相关性分析:在瘢痕癌组织中,Cyclin D1与CDK4、p21与CDK4的表达均呈正相关。结论瘢痕癌的发生与Cyclin D1、CDK4的异常表达有关,Cyclin D1可能是通过与CDK4结合形成复合物,促进细胞周期G1/S期转化,导致细胞异常增生,瘢痕癌发生。瘢痕癌中Cyclin D1-CDK4复合物活性的抑制调控,可能是CKI家族的其他成员或者有CKI家族以外的其他抑制调控因子。
[Abstract]:Objective the dysregulation of cell cycle is an important factor in tumorigenesis of cell proliferation. To investigate the expression and significance of cell cycle regulation system related factor Cyclin D1-CDK4-p21 in scar carcinoma. Methods paraffin embedded specimens were collected from Department of Pathology, Zunyi Medical College and Department of Pathology of the Fifth affiliated Hospital of Sun Yat-sen University from 2005 to 2011. The specimens were divided into three groups: scar carcinoma group, pathological scar group and normal skin group. The expression of Cyclin D1-CDK4p21 protein in scar carcinoma, pathological scar and normal skin was detected by histochemical method. In situ hybridization was used to detect the expression of Cyclin D1 mRNA-CDK4 mRNAp21 mRNA in three groups of tissues. The average optical density (expression intensity) and positive area (expression level) were calculated by correlation analysis. Results 1Cyclin D1 mRNA-CDK4 mRNAp21 protein and Cyclin D1 mRNA-CDK4 mRNAp21 mRNA were strongly expressed in scar carcinoma, weakly positive in pathological scar epithelium and weakly positive or negative in normal skin epidermis. The expression of CDK4 protein in scar cancer group was 0.273 卤0.024) and the expression level was 0.159 卤0.036), which was higher than that in normal skin group (0.194 卤0.013) 0.053 卤0.086 and pathological scar group (0.214 卤0.026) 0.061 卤0.014). The expression level of CDK4 mRNA in scar carcinoma group was 0.281 卤0.033 and 0.207 卤0.039) higher than that in normal skin group (0.195 卤0.012) and pathological scar group (0.235 卤0.021) 0.080 卤0.032). The expression intensity of Cyclin D1 protein in scar cancer group was 0.262 卤0.023 (0.141 卤0.036) higher than that in normal skin group (0.169 卤0.012 卤0.039 卤0.095) and pathological scar group (0.176 卤0.039 卤0.065 卤0.013). The expression intensity of Cyclin D1mRNA in scar carcinoma group was 0.264 卤0.031 and 0.201 卤0.041) higher than that in normal skin group (0.179 卤0.022) and pathological scar group (0.193 卤0.021 卤0.068 卤0.035). The expression intensity of p21 protein in scar carcinoma group was higher than that in normal skin group (0. 052 卤0. 020) and pathological scar group (0. 062 卤0. 021 ~ 0. 214 卤0. 032), and the expression intensity of p21 mRNA in scar carcinoma group was 0. 227 卤0. 059) higher than that in normal skin group (0. 072 卤0. 0440.203 卤0. 024) and pathological scar group (0. 075 卤0. 041 卤0. 0223 卤0. 021). The difference was statistically significant (P 0.01), but there was no significant difference between the pathological scar group and the normal skin group. The correlation analysis showed that the expression of Cyclin D1, CDK4p21 and CDK4 were positively correlated in the scar carcinoma tissues. Conclusion the occurrence of scar carcinoma is related to the abnormal expression of Cyclin D1 + CDK4, which may be related to the formation of complex with CDK4 and promote the transformation of G 1 / S phase of cell cycle, leading to abnormal proliferation of cells and carcinogenesis of scar. The inhibitory regulation of Cyclin D1-CDK4 complex activity in scar carcinoma may be other members of the CKI family or other inhibitory regulators other than the CKI family.
【作者单位】: 遵义医学院珠海校区病理学教研室;中山大学附属第五医院病理科;
【基金】:贵州省科技攻关项目(2010-3080)
【分类号】:R739.5
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