MiR-221 promotes trastuzumab-resistance and metastasis in HER2-positive breast cancers by targeting PTEN |
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| Authors: | Xingming Ye Wendong Bai Huayu Zhu Xiao Zhang Ying Chen Lei Wang Angang Yang Jing Zhao Lintao Jia |
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| Affiliation: | 1.State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular, Biology, Fourth Military Medical University, Xi’an 710032, China;2.Fujian Provincial Cancer Hospital, the Teaching Hospital of Fujian Medical University, Fuzhou 350014, China;3.Department of Immunology, Fourth Military Medical University, Xi’an 710032, China;4.Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, China |
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| 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. [BMB Reports 2014; 47(5): 268-273]. |
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| Keywords: | Breast cancer erbB2/HER2 Metastasis miR-221 PTEN Trastuzumab resistance |
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