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KMID : 0624620140470050268
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BMB Reports
2014 Volume.47 No. 5 p.268 ~ p.273
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MiR-221 promotes trastuzumab-resistance and metastasis in HER2-positive breast cancers by targeting PTEN
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Ye Xingming
Bai Wendong
Zhu Huayu
Zhang Xiao
Chen Ying
Wang Lei
Yang Angang
Zhao Jing
Jia Lintao
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Abstract
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HER2-overexpressing breast cancers are characterized by frequent distant metastasis and often develop resistance after short-term effective treatment with the monoclonal antibody drug, trastuzumab. Here, we found that the oncogenic miRNA, miR-221, inhibited apoptosis, induced trastuzumab resistance and promoted metastasis of HER2-positive breast cancers. The tumor suppressor PTEN was identified as a miR-221 target; overexpression of PTEN abrogated the aforementioned miR-221-induced malignant phenotypes of the cells. These findings indicate that miR-221 may promote trastuzumab resistance and metastasis of HER2-positive breast cancers by targeting PTEN, suggesting its role as a potential biomarker for progression and poor prognosis, and as a novel target for trastuzumab-combined treatment of breast cancers.
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KEYWORD
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Breast cancer, erbB2/HER2, Metastasis, miR-221, PTEN, Trastuzumab resistance
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