端粒酶基因与凋亡相关基因在乳腺导管非典型增生中表达的相关性研究

背景与目的:近年研究表明端粒酶的激活及凋亡抑制基因的过度表达与多种肿瘤发生有关,本研究观察端粒酶基因(hTR,hTRT)、凋亡相关基因(p53,bcl-2)在乳腺导管非典型增生中的表达及相互关系,旨在探讨端粒酶活性及凋亡相关基因的变化在乳腺导管非典型增生上皮癌变过程中的作用和意义。方法:应用原位杂交方法检测端粒酶基因(hTR,hTRT)和凋亡相关基因(p53,bcl-2)mRNA在44例乳腺导管非典型增生组织中的表达,应用免疫组化方法检测p53蛋白在上述病例中的表达,并与6例良性乳腺增生及26例乳腺癌病例进行了比较。结果:端粒酶基因(hTR,hTRTmRNA)在乳腺导管重度非典型增生组织中表达增强(60.9%,52.1%),其表达与在轻、中度非典型增生(22.2%,11.1%;33.3%,25.0%),乳腺癌(88.5%,80.8%)组织中的表达差异显著(P<0.05)。p53mRNA在乳腺导管非典型增生组织中的表达随着异型性的增加而下降(轻度:55.6%;中度:41.7%;重度:26.1%),而p53蛋白则相应增加(轻度:11.1%;中度:25.0%;重度:34.8%)。bcl-2在乳腺导管非典型增生组织中呈中度表达,其中以在重度非典型增生组织中表达明显。结论:端粒酶基因(hTR,hTRT)的表达与乳腺非典型增生细胞的恶性转化密切相关,同时可检测到p53mRNA的表达缺失、p53蛋白突变及bcl-2mRNA的过表达,且表达水平与端

Relationship between expressions of telomerase genes and apoptosis related genes in mammary ductal atypical hyperplasia

Background &Objective:Recent studies showed that the activ ating of telomerase and excessive expression of apoptosis suppressor genes were related to the developmen t of many tumors.This study was desig ned to investigate the expression of telom erase genes(hTR,hTRT)and apoptosis related genes(p53,bcl-2)in mammary atypical ductal hyperplasia for exploring th e change of telomerase activity and a poptosis related genes in the process of mammary ductal dysplasia to malignant transformation.Method:Expressions of telomerase genes(hTR,hTRT)and apoptosis related genes(p53,bcl-2)were detected by in situ hybridizati on and expression of the mutant p53pr otein was detected by immunohistochemistry were detecte d in 44patients with mammary atypical ductal hyperplasia,those expression were compared with those of the 6benign hyperplasia and 26breast carcinoma.Result:High expressions of telomerase genes(hTR,hTRT mRNA)in severe atypical ductal hyperplasia(60.9%,52.1%)is of significantly difference from that in mild-medium atypical ductal hyperp lasia(22.2%,11.1%;33.3%,25.0%)and breast cancer(88.5%,80.8%).The upgrading of atypia link with decrea sed expression of wild p53 485mRNA(mild:55.6%;medium:41.7%;severe:26.1%)and increased expression of the muta nt p53protein(mild:11.1%;medium:25.0%;severe:34.8%).As for bcl-2mRNA,it shows moderate expression,especially in severe atypical ductal hyperplasia.Conclusion:Our study revealed significant corr elation between expressions of telo merase genes(hTR,hTRT)and the state of malignant transform ation in mammary atypical ductal hyp erplasia.Decreased expression of wild p53gene,increased expression of mutant p53protein,and overexpre ssion of bcl-2gene were associated w ith telomerase.