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http://dx.doi.org/10.5483/BMBRep.2014.47.5.165

MiR-221 promotes trastuzumab-resistance and metastasis in HER2-positive breast cancers by targeting PTEN  

Ye, Xingming (State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular, Biology, Fourth Military Medical University)
Bai, Wendong (Department of Immunology, Fourth Military Medical University)
Zhu, Huayu (State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular, Biology, Fourth Military Medical University)
Zhang, Xiao (State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular, Biology, Fourth Military Medical University)
Chen, Ying (Fujian Provincial Cancer Hospital, the Teaching Hospital of Fujian Medical University)
Wang, Lei (State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular, Biology, Fourth Military Medical University)
Yang, Angang (Department of Immunology, Fourth Military Medical University)
Zhao, Jing (State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular, Biology, Fourth Military Medical University)
Jia, Lintao (State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular, Biology, Fourth Military Medical University)
Publication Information
BMB Reports / v.47, no.5, 2014 , pp. 268-273 More about this Journal
Abstract
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.
Keywords
Breast cancer; erbB2/HER2; Metastasis; miR-221; PTEN; Trastuzumab resistance;
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