论文部分内容阅读
目的 了解细胞周期p2 1waf1/cip1调控途径中p53、p2 1waf1/cip1、cyclinD1、cyclinE基因在乳腺癌发病机制中作用及相互间关系。方法 用免疫组化方法于 17例乳腺良性组织、19例癌前病变、69例乳腺癌 ( 2 0例导管内癌、4 9例浸润性导管癌 )中检测 4种基因蛋白表达 ,原位RNA分子杂交、原位DNA分子杂交方法于 2 5例乳腺癌、15例癌前病变 (大部为cyclinD1蛋白过表达 )中检测cyclinD1mRNA水平及基因状况。结果 ①p53在良性、癌前病变组织中失表达 ,在乳腺癌中阳性表达率为 2 8% ;②p2 1表达与 p53表达无负相关性 ;③p2 1在乳腺癌中过表达率为 2 9% ;cyclinD1、cyclinE过表达率为 4 6%、51% ,显著高于癌前病变及良性组织 ;cyclinD1过表达与淋巴结转移、cyclinE过表达与肿块大小呈正相关 ;④cyclinD1蛋白过表达的乳腺癌中其相关的基因扩增率为 32 % ;⑤p2 1表达与cyclinD1、cyclinE表达正相关。结论 ①突变型 p53基因参与乳腺癌发生 ;②乳腺癌中 p2 1表达不完全依赖于野生型 p53基因 ;③正、负性调控因子 p2 1、cyclinD1、cyclinE基因表达异常及cyclinD1基因异常是乳腺癌早期频发的分子事件 ,参与乳腺癌发生发展 ,证实了周期失控是肿瘤发生的重要机制 ;④基因扩增是cyclinD1mRNA过表达及蛋白过表达的分子机?
Objective To investigate the role of p53, p2 1waf1/cip1, cyclinD1, and cyclinE genes in the pathogenesis of breast cancer and their relationship with each other in the p2 1waf1/cip1 regulatory pathway. Methods Immunohistochemistry was used to detect the expression of four gene proteins in 17 cases of benign breast tissue, 19 cases of precancerous lesions, 69 cases of breast cancer (20 cases of ductal carcinoma and 49 cases of invasive ductal carcinoma). Molecular hybridization and in situ DNA hybridization were used to detect cyclinD1 mRNA levels and gene status in 25 cases of breast cancer and 15 cases of precancerous lesions (mostly cyclinD1 protein overexpression). Results 1 The expression of p53 was deregulated in benign and precancerous lesions. The positive expression rate was 28% in breast cancer. There was no negative correlation between 2p21 expression and p53 expression. The overexpression rate of 3p21 in breast cancer was 29%. The overexpression rates of cyclinD1 and cyclinE were 46% and 51%, which were significantly higher than precancerous lesions and benign tissues. CyclinD1 overexpression was positively correlated with lymph node metastasis, cyclinE overexpression and tumor size. 4 CyclinD1 protein overexpression was associated with breast cancer. The gene amplification rate was 32%; the expression of 5p21 was positively correlated with the expression of cyclinD1 and cyclinE. Conclusion 1 The mutant p53 gene is involved in the carcinogenesis of breast cancer; 2 The expression of p21 in breast cancer is not completely dependent on the wild-type p53 gene; 3 The abnormal expression of positive and negative regulators p21, cyclinD1 and cyclinE genes and abnormal cyclinD1 gene are breast cancers. The frequent occurrence of molecular events involved in the development of breast cancer confirmed the out-of-control cycle as an important mechanism of tumorigenesis. 4 Gene amplification is a molecular mechanism for overexpression of cyclinD1 mRNA and protein overexpression.