C-FLIP(L) 促进 HER2 阳性乳腺癌对 TRAIL 的耐药性。
C-FLIP(L) contributes to TRAIL resistance in HER2-positive breast cancer.
机构信息
Department of Pathology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China.
Princess Margaret Cancer Centre, University Health Network and University of Toronto, Toronto, Ontario M5G 2M9, Canada.
出版信息
Biochem Biophys Res Commun. 2014 Jul 18;450(1):267-73. doi: 10.1016/j.bbrc.2014.05.106. Epub 2014 Jun 6.
Breast cancers with HER2 amplification have a poorer prognosis than the luminal phenotypes. TRAIL activates apoptosis upon binding its receptors in some but not all breast cancer cell lines. Herein, we investigated the expression pattern of c-FLIP(L) in a cohort of 251 invasive breast cancer tissues and explored its potential role in TRAIL resistance. C-FLIP(L) was relatively high-expressed in HER2-positive breast cancer in comparison with other molecular subtypes, co-expressed with TRAIL death receptors, and inversely correlated with the apoptosis index. Downregulation of c-FLIP(L) sensitized SKBR3 cells to TRAIL-induced apoptosis in a concentration- and time-dependent manner and enhanced the activities and cleavages of caspase-8 and caspase-3, without altering the surface expression of death receptors. Together, our results indicate that c-FLIP(L) promotes TRAIL resistance and inhibits caspase-3 and caspase-8 activation in HER2-positive breast cancer.
具有 HER2 扩增的乳腺癌比 luminal 表型预后更差。TRAIL 在与其受体结合后会在一些但不是所有乳腺癌细胞系中激活细胞凋亡。在此，我们研究了 251 例浸润性乳腺癌组织中 c-FLIP(L)的表达模式，并探讨了其在 TRAIL 耐药中的潜在作用。与其他分子亚型相比，c-FLIP(L)在 HER2 阳性乳腺癌中表达较高，与 TRAIL 死亡受体共表达，并与凋亡指数呈负相关。c-FLIP(L)下调以浓度和时间依赖的方式使 SKBR3 细胞对 TRAIL 诱导的细胞凋亡敏感，并增强了 caspase-8 和 caspase-3 的活性和裂解，而不改变死亡受体的表面表达。总之，我们的结果表明，c-FLIP(L)促进了 HER2 阳性乳腺癌中 TRAIL 的耐药性，并抑制了 caspase-3 和 caspase-8 的激活。
Zotero 插件