IMP3 Protein Promotes Chemoresistance in Breast Cancer Cells by Regulating Breast Cancer Resistance Protein (ABCG2) Expression
IMP3 Protein Promotes Chemoresistance in Breast Cancer Cells by Regulating Breast Cancer Resistance Protein (ABCG2) Expression
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DOI：
10.1074/jbc.c112.442319
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发表时间：
2013-05-03
影响因子：
4.8
通讯作者：
Mercurio, Arthur M.
中科院分区：
文献类型：
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作者：
Samanta, Sanjoy;Pursell, Bryan;Mercurio, Arthur M.
IMP3是胰岛素样生长因子II(IGF-II)信使核糖核酸结合蛋白(IMP)家族中的一员，在对多种化疗药物耐药的三阴性乳腺癌中优先表达。然而，它影响乳腺癌的机制还没有被阐明。基于这些观察，我们推测了IMP3在化疗耐药中的作用。在三阴性乳腺癌细胞中IMP3表达缺失显着增加了它们对阿霉素和米托蒽醌的敏感性，但对紫杉醇的敏感性不明显。考虑到阿霉素和米托蒽醌是由乳腺癌耐药蛋白(BCRP)排出的，我们评估了IMP3是否调节BCRP。结果表明，IMP3能与BCRP mRNA结合并调节BCRP的表达。这些发现意义重大，因为它们提供了对IMP3促进侵袭性癌症的机制的洞察，并突显了将这种mRNA结合蛋白作为靶点用于癌症临床治疗的潜力。
IMP3, a member of a family of insulin-like growth factor II (IGF-II) mRNA-binding proteins (IMPs), is expressed preferentially in triple-negative breast cancers, which are resistant to many chemotherapeutics. However, the mechanisms by which it impacts breast cancer have not been elucidated. We hypothesized a role for IMP3 in chemoresistance based on these observations. Depletion of IMP3 expression in triple-negative breast cancer cells increased their sensitivity to doxorubicin and mitoxantrone significantly but not to taxol. Given that doxorubicin and mitoxantrone are effluxed by breast cancer resistance protein (BCRP), we assessed whether IMP3 regulates BCRP. The data obtained demonstrate that IMP3 binds to BCRP mRNA and regulates BCRP expression. These findings are significant because they provide insight into the mechanism by which IMP3 contributes to aggressive cancers, and they highlight the potential for targeting this mRNA-binding protein for the clinical management of cancer.