MADD knock-down enhances doxorubicin and TRAIL induced apoptosis in breast cancer cells.
MADD knock-down enhances doxorubicin and TRAIL induced apoptosis in breast cancer cells.
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DOI：
10.1371/journal.pone.0056817
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Prabhakar BS
中科院分区：
文献类型：
--
作者：
Turner A;Li LC;Pilli T;Qian L;Wiley EL;Setty S;Christov K;Ganesh L;Maker AV;Li P;Kanteti P;Das Gupta TK;Prabhakar BS
IG20基因的MADD亚型在不同类型的肿瘤组织和细胞系中过表达，是细胞凋亡的负调控因子。因此，我们推测MADD可能在人乳腺癌组织中过表达，并且MADD的下调可能与化疗或TRAIL诱导的乳腺癌细胞的凋亡有协同作用。乳腺组织芯片分析显示，相对于良性组织，MADD在导管癌和浸润性癌中过度表达。MADD基因敲除导致人乳腺癌细胞自发性凋亡增强。此外，与单独使用TRAIL或阿霉素相比，MADD基因敲除后再用TRAIL或阿霉素治疗会导致细胞死亡增加。细胞死亡增强是caspase-8激活增强的次要原因。这些数据表明，降低乳腺癌MADD表达或功能的策略可能被用来提高肿瘤细胞对TRAIL和阿霉素诱导的细胞凋亡的敏感性。
The Map kinase Activating Death Domain containing protein (MADD) isoform of the IG20 gene is over-expressed in different types of cancer tissues and cell lines and it functions as a negative regulator of apoptosis. Therefore, we speculated that MADD might be over-expressed in human breast cancer tissues and that MADD knock-down might synergize with chemotherapeutic or TRAIL-induced apoptosis of breast cancer cells. Analyses of breast tissue microarrays revealed over-expression of MADD in ductal and invasive carcinomas relative to benign tissues. MADD knockdown resulted in enhanced spontaneous apoptosis in human breast cancer cell lines. Moreover, MADD knockdown followed by treatment with TRAIL or doxorubicin resulted in increased cell death compared to either treatment alone. Enhanced cell death was found to be secondary to increased caspase-8 activation. These data indicate that strategies to decrease MADD expression or function in breast cancer may be utilized to increase tumor cell sensitivity to TRAIL and doxorubicin induced apoptosis.
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影响因子：
4.8
作者：
Li, Peifeng;Jayarama, Shankar;Prabhakar, Bellur S.
通讯作者：
Prabhakar, Bellur S.
影响因子：
14.5
作者：
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通讯作者：
El-Deiry, WS
影响因子：
32.4
作者：
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通讯作者：
Walczak, H
影响因子：
56.9
作者：
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通讯作者：
Dixit, VM
影响因子：
8
作者：
Lin, TY;Huang, XF;Fang, BL
通讯作者：
Fang, BL