Song Min, Li Bai-lin, Mi Xiao-yi, Gao Ying-xian, Song Ji-ye
Department of Pathology, College of Basic Medical Sciences, China Medical University, Shenyang 110001, P. R. China.
Ai Zheng. 2002 May;21(5):484-8.
BACKGROUND & OBJECTIVE: Recent studies showed that the activating of telomerase and excessive expression of apoptosis suppressor genes were related to the development of many tumors. This study was designed to investigate the expression of telomerase genes (hTR, hTRT) and apoptosis related genes (p53, bcl-2) in mammary atypical ductal hyperplasia for exploring the change of telomerase activity and apoptosis related genes in the process of mammary ductal dysplasia to malignant transformation.
Expressions of telomerase genes (hTR, hTRT) and apoptosis related genes (p53, bcl-2) were detected by in situ hybridization and expression of the mutant p53 protein was detected by immunohistochemistry were detected in 44 patients with mammary atypical ductal hyperplasia, those expression were compared with those of the 6 benign hyperplasia and 26 breast carcinoma.
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 hyperplasia (22.2%, 11.1%; 33.3%, 25.0%) and breast cancer (88.5%, 80.8%). The upgrading of atypia link with decreased expression of wild p53 mRNA (mild: 55.6%; medium: 41.7%; severe: 26.1%) and increased expression of the mutant p53 protein (mild: 11.1%; medium: 25.0%; severe: 34.8%). As for bcl-2 mRNA, it shows moderate expression, especially in severe atypical ductal hyperplasia.
Our study revealed significant correlation between expressions of telomerase genes (hTR, hTRT) and the state of malignant transformation in mammary atypical ductal hyperplasia. Decreased expression of wild p53 gene, increased expression of mutant p53 protein, and overexpression of bcl-2 gene were associated with telomerase.
近期研究表明,端粒酶激活及凋亡抑制基因过度表达与多种肿瘤的发生发展相关。本研究旨在探讨端粒酶基因(hTR、hTRT)及凋亡相关基因(p53、bcl-2)在乳腺非典型导管增生中的表达情况,以探索乳腺导管发育异常至恶性转化过程中端粒酶活性及凋亡相关基因的变化。
采用原位杂交法检测44例乳腺非典型导管增生患者端粒酶基因(hTR、hTRT)及凋亡相关基因(p53、bcl-2)的表达,免疫组织化学法检测突变型p53蛋白的表达,并与6例乳腺良性增生及26例乳腺癌患者进行比较。
重度非典型导管增生中端粒酶基因(hTR、hTRT mRNA)的高表达率(60.9%,52.1%)与轻-中度非典型导管增生(22.2%,11.1%;33.3%,25.0%)及乳腺癌(88.5%,80.8%)相比有显著差异。非典型程度的升级与野生型p53 mRNA表达降低(轻度:55.6%;中度:41.7%;重度:26.1%)及突变型p53蛋白表达增加(轻度:11.1%;中度:25.0%;重度:34.8%)相关。至于bcl-2 mRNA,呈中度表达,尤其在重度非典型导管增生中。
本研究揭示端粒酶基因(hTR、hTRT)表达与乳腺非典型导管增生的恶性转化状态之间存在显著相关性。野生型p53基因表达降低、突变型p53蛋白表达增加及bcl-2基因过表达均与端粒酶相关。