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MEK inhibitor effective against proliferation in breast cancer cell

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Tumor Biology

Abstract

The targeted small-molecule drug AZD6244 is an allosteric, ATP-noncompetitive inhibitor of MEK1/2 that has shown activity against several malignant tumors. Here, we report that AZD6244 repressed cell growth and induced apoptosis and G1-phase arrest in the breast cancer cell lines MDA-MB-231 and HCC1937. Using microRNA (miRNA) arrays and quantitative RT-PCR, we found that miR-203 was up-regulated after AZD6244 treatment. In accordance with bioinformatics and luciferase activity analyses, CUL1 was found to be the direct target of miR-203. Furthermore, miR-203 inhibition and CUL1 overexpression reversed the cytotoxicity of AZD6244 on the MDA-MB-231 and HCC1937 cells. Collectively, our data indicate that miR-203 mediates the AZD6244-induced cytotoxicity of breast cancer cells and that the MEK/ERK/miR-203/CUL1 signaling pathway may participate in this process.

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Acknowledgments

This study was supported by the National Natural Science Foundation of China (81072176 and 81372873).

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Authors and Affiliations

  1. Oncology Department of Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, No 600 Yishan Road Xuhui, Shanghai City, China, 200233

    Yan Zhou, Hai-yan Hu, Jing-jing Sha & Yang Yao

  2. Genetic Engineering Institute of Southern Medical University, No 155 Guangzhou Road Baiyun, Guangzhou City, Guangdong Province, China, 510515

    Wei Meng & Ling Jiang

  3. Hematology Department of Zhujiang Hospital affiliated to Southern Medical University, No 253 Gongye Road Haizhu, Guangzhou City, Guangdong Province, China, 510282

    Xing Zhang & Zhigang Lu

Authors
  1. Yan Zhou
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  2. Hai-yan Hu
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  4. Ling Jiang
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Correspondence to Zhigang Lu or Yang Yao.

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Yan Zhou and Hai-yan Hu, the first authors, contributed equally to this work.

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Zhou, Y., Hu, Hy., Meng, W. et al. MEK inhibitor effective against proliferation in breast cancer cell. Tumor Biol. 35, 9269–9279 (2014). https://doi.org/10.1007/s13277-014-1901-5

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