Poonepalli Anuradha, Banerjee Birendranath, Ramnarayanan Kalpana, Palanisamy Nallasivam, Putti Thomas Choudary, Hande M Prakash
Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Genes Chromosomes Cancer. 2008 Dec;47(12):1098-109. doi: 10.1002/gcc.20608.
A study was undertaken to correlate telomere dysfunction and genomic instability with the histopathological grades and the estrogen and progesterone receptor status in breast cancer. Sixty-one archived breast tissues (38 cancer tissues and 23 paired normal tissues) were used in the study. The breast tumor tissues showed significantly shorter telomeres (7.7 kb) compared with the paired adjacent tissues (9.0 kb) by Southern blot analysis. Moreover, telomere shortening was more significant in Grade III tumors than in the Grade II tumors (P = 0.05). Quantitative fluorescence in situ hybridization on paraffin tissue sections revealed a similar trend in telomere shortening. Telomere attrition was associated with telomere dysfunction as revealed by the presence of significantly higher anaphase bridges in tumor cells which was tumor grade dependent. Furthermore, estrogen receptive negative tumors displayed higher anaphase and internuclear bridges. Selected samples from each grade showed greater genomic imbalances in the higher grades than the lower grade tumors as detected by array-comparative genomic hybridization. Telomerase activity was found to be higher in the higher grades (Grade II and III) compared with the lower grade (Grade I). The average mRNA expression of TRF1 and POT1 was lower in the tumor tissues than in the normal tissues. Tankyrase 1 mRNA expression showed a grade-dependent increase in tumor tissues and its expression was also high in estrogen and progesterone negative tumors. The data support the notion that telomere dysfunction might be of value as a marker of aggressiveness of the tumors in breast cancer patients.
开展了一项研究，旨在将端粒功能障碍和基因组不稳定性与乳腺癌的组织病理学分级以及雌激素和孕激素受体状态相关联。该研究使用了61份存档的乳腺组织（38份癌组织和23份配对的正常组织）。通过Southern印迹分析，与配对的相邻组织（9.0 kb）相比，乳腺肿瘤组织显示出明显更短的端粒（7.7 kb）。此外，III级肿瘤中的端粒缩短比II级肿瘤更显著（P = 0.05）。石蜡组织切片上的定量荧光原位杂交显示出端粒缩短的类似趋势。如肿瘤细胞中明显更高的后期桥的存在所揭示的，端粒磨损与端粒功能障碍相关，且后期桥的出现与肿瘤分级有关。此外，雌激素受体阴性肿瘤显示出更高的后期桥和核间桥。通过阵列比较基因组杂交检测，每个分级的选定样本显示，高分级肿瘤比低分级肿瘤存在更大的基因组失衡。发现端粒酶活性在高分级（II级和III级）肿瘤中比低分级（I级）肿瘤中更高。肿瘤组织中TRF1和POT1的平均mRNA表达低于正常组织。端锚聚合酶1 mRNA表达在肿瘤组织中呈分级依赖性增加，且在雌激素和孕激素阴性肿瘤中其表达也很高。这些数据支持这样一种观点，即端粒功能障碍可能作为乳腺癌患者肿瘤侵袭性的标志物具有一定价值。
