Endonuclease G promotes cell death of non-invasive human breast cancer cells
Endonuclease G promotes cell death of non-invasive human breast cancer cells
复制标题
DOI：
10.1016/j.yexcr.2006.09.012
复制
发表时间：
2006-12-10
影响因子：
3.7
通讯作者：
Shah, Sudhir V.
中科院分区：
文献类型：
--
作者：
Basnakian, Alexei G.;Apostolov, Eugene O.;Shah, Sudhir V.
乳腺癌细胞的侵袭性被证明与抑制细胞凋亡的能力有关。细胞死亡DNA酶/核酸内切酶的作用与乳腺癌细胞的侵袭性之间的关系以前没有研究过。我们比较了七个人乳腺癌细胞系中不同的侵袭力和分化水平的核酸内切酶的活性。通过基于基质胶的体外测定证实细胞系的侵袭性。分化的非侵袭性（WDNI）细胞系中的总核酸内切酶活性高于低分化的侵袭性（PDI）细胞系。EndoG的表达与雌激素受体的表达程度密切相关，与波形蛋白和基质金属蛋白酶-13呈负相关。EndoG阳性的WDNI细胞对依托泊苷或喜树碱诱导的细胞死亡比EndoG阴性的PDI细胞更敏感。EndoG沉默可抑制足叶乙甙诱导的SK-BR-3 WDNI细胞死亡。人导管原位癌表达高水平的EndoG，而浸润性髓样癌和导管癌的EndoG表达显著降低。这与通过TUNEL测定测量的细胞凋亡减少相关。我们的研究结果表明，EndoG在非侵袭性乳腺癌细胞中的存在决定了它们对细胞凋亡的敏感性，这可以考虑用于开发癌症治疗的化疗策略。(c)2006年爱思唯尔公司All rights reserved.
The invasiveness of breast cancer cells was shown to be associated with the suppressed ability to develop apoptosis. The role of cell death DNases/endonucleases has not been previously examined in relation with the invasiveness of breast cancer cells. We have compared the activity of the endonucleases in seven human breast cancer cell lines different in the level of invasiveness and differentiation. The invasiveness of cell lines was confirmed by an in vitro Matrigel-based assay. The total endonuclease activity in the differentiated non-invasive (WDNI) cell lines was higher than that in the poorly differentiated invasive (PDI) cells. The expression of EndoG strongly correlated with the degree of estrogen receptor expression and showed an inverse correlation with vimentin and matrix metalloproteinase-13. The EndoG-positive WDNI cells were more sensitive to etoposide- or camptothecin-induced cell death than EndoG-negative PDI cells. Silencing of EndoG caused inhibited of SK-BR-3 WDNI cell death induced by etoposide. Human ductal carcinomas in situ expressed high levels of EndoG, while invasive medullar and ductal carcinomas had significantly decreased expression of EndoG. This correlated with decreased apoptosis as measured by TUNEL assay. Our findings suggest that the presence of EndoG in non-invasive breast cancer cells determines their sensitivity to apoptosis, which may be taken into consideration for developing the chemotherapeutic strategy for cancer treatment. (c) 2006 Elsevier Inc. All rights reserved.