ABCG2 expression and side population abundance regulated by a transforming growth factor β-directed epithelial-mesenchymal transition
ABCG2 expression and side population abundance regulated by a transforming growth factor β-directed epithelial-mesenchymal transition
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DOI：
10.1158/0008-5472.can-07-2545
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发表时间：
2008-02-01
期刊：
影响因子：
11.2
通讯作者：
Assoian, Richard K.
中科院分区：
文献类型：
--
作者：
Yin, Liqun;Castagnino, Paola;Assoian, Richard K.
我们在这里描述了ABCG2在MCF7人乳腺癌细胞中的表达和侧群(SP)丰度的调节。与非SP细胞相比，纯化的MCF7 SP中ABCG2的mRNA和蛋白水平升高，与ABCG2特异性抑制剂或ABCG2短干扰RNA孵育可消除MCF7 SP。纯化的MCF7 SP可以在培养中产生既含有SP细胞又含有非SP细胞的异质性群体。体内致瘤性实验表明，纯化的MCF7 SP在小鼠乳腺的定植能力增强。重要的是，MCF7 SP被转化生长因子-β(转化生长因子-β)导向的上皮-间充质转化(EMT)所耗尽，这种作用与ABCG2基因表达的强烈下调以及对米托蒽醌的敏感性增加有关。去除转化生长因子-β后，ABCG2的表达和SP丰度恢复，细胞恢复为上皮表型。E-钙粘附素基因敲除也降低了SP的丰度，但这种作用并不伴随ABCG2基因或蛋白的丢失。我们的结论是，ABCG2在MCF7细胞中的表达在EMT过程中受到调节，EMT效应反映了E-钙粘蛋白对ABCG2功能的翻译后调节以及ABCG2基因的转录抑制。
We describe here the regulation of ABCG2 expression and side population (SP) abundance in MCF7 human breast cancer cells. The level of ABCG2 mRNA and protein were increased in purified MCF7 SP relative to non-SP cells, and incubation with an ABCG2-specific inhibitor or ABCG2 short interfering RNA eliminated the MCF7 SP. The purified MCF7 SP could generate a heterogeneous population containing both SP and non-SP cells in culture. In vivo tumorigenicity experiments showed that the purified MCF7 SP has an increased ability to colonize the mouse mammary gland. Importantly, the MCF7 SP was depleted by a transforming growth factor-beta (TGF beta)-directed epithelial-mesenchymal transition (EMT), and this effect was associated with a strong down-regulation of ABCG2 gene expression, and an increased sensitivity to mitoxantrone. ABCG2 expression and SP abundance were restored upon the removal of transforming growth factor-beta and reversion of the cells to an epithelial phenotype. Knock-down of E-cadherin also reduced SP abundance, but this effect was not accompanied by the loss of ABCG2 mRNA or protein. We conclude that ABCG2 expression in MCF7 cells is regulated during an EMT, and that the EMT effect reflects posttranslational regulation of ABCG2 function by E-cadherin as well as transcriptional repression of the ABCG2 gene.