c-FLIP gene silencing eliminates tumor cells in breast cancer xenografts without affecting stromal cells.

c-FLIP gene silencing eliminates tumor cells in breast cancer xenografts without affecting stromal cells.
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DOI:
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发表时间:
2009-10
影响因子:
2
通讯作者:
T. W. Day;A. Sinn;Su Huang;K. Pollok;G. Sandusky;A. Safa
T. W. Day;A. Sinn;Su Huang;K. Pollok;G. Sandusky;A. Safa
中科院分区:
医学4区
文献类型:
--
作者:
T. W. Day;A. Sinn;Su Huang;K. Pollok;G. Sandusky;A. Safa

文献摘要

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细胞FLICE样抑制蛋白(c-FLIP)是死亡受体介导的细胞凋亡的抑制剂,通过阻断caspase-8的激活发挥其抗细胞凋亡功能。我们最近发现,在体外生长的 MCF-7 乳腺癌细胞中,siRNA 介导的 c-FLIP 敲低可引发细胞凋亡。本研究的目的是确定 MCF-7 乳腺癌异种移植物中 c-FLIP 的体内敲低是否影响肿瘤活力。肿瘤切片中 c-FLIP 的免疫组织化学检测表明,c-FLIP 的敲低消除了乳腺癌异种移植物内的肿瘤细胞,而不影响正常基质细胞和成纤维细胞。这些结果表明c-FLIP是乳腺癌生长所必需的,并且是治疗乳腺癌的相关治疗靶点。
Cellular FLICE-like inhibitory protein (c-FLIP) is an inhibitor of death receptor-mediated apoptosis and exerts its anti-apoptotic function by blocking the activation of caspase-8. We recently showed that the siRNA-mediated knockdown of c-FLIP in MCF-7 breast cancer cells growing in vitro triggered apoptosis. The aim of this study was to determine if the in vivo knockdown of c-FLIP in MCF-7 breast cancer xenografts affected tumor viability. Immunohistochemical detection of c-FLIP in the tumor sections revealed that the knockdown of c-FLIP eliminated the neoplastic cells within the breast cancer xenografts without affecting the normal stromal and fibroblastic cells. These results indicate that c-FLIP is required for breast cancer growth and is a relevant therapeutic target for the treatment of breast cancer.