MiR-221 promotes trastuzumab-resistance and metastasis in HER2-positive breast cancers by targeting PTEN
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HER2-overexpressing breast cancers are characterized byfrequent distant metastasis and often develop resistance aftershort-term effective treatment with the monoclonal antibodydrug, trastuzumab. Here, we found that the oncogenic miRNA,miR-221, inhibited apoptosis, induced trastuzumab resistanceand promoted metastasis of HER2-positive breast cancers. Thetumor suppressor PTEN was identified as a miR-221 target;overexpression of PTEN abrogated the aforementionedmiR-221-induced malignant phenotypes of the cells. Thesefindings indicate that miR-221 may promote trastuzumabresistance and metastasis of HER2-positive breast cancers bytargeting PTEN, suggesting its role as a potential biomarker forprogression and poor prognosis, and as a novel target fortrastuzumab-combined treatment of breast cancers.
Abstract
HER2-overexpressing breast cancers are characterized byfrequent distant metastasis and often develop resistance aftershort-term effective treatment with the monoclonal antibodydrug, trastuzumab. Here, we found that the oncogenic miRNA,miR-221, inhibited apoptosis, induced trastuzumab resistanceand promoted metastasis of HER2-positive breast cancers. Thetumor suppressor PTEN was identified as a miR-221 target;overexpression of PTEN abrogated the aforementionedmiR-221-induced malignant phenotypes of the cells. Thesefindings indicate that miR-221 may promote trastuzumabresistance and metastasis of HER2-positive breast cancers bytargeting PTEN, suggesting its role as a potential biomarker forprogression and poor prognosis, and as a novel target fortrastuzumab-combined treatment of breast cancers.
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