Tumor Biol. DOI 10.1007/s13277-014-1901-5
RESEARCH ARTICLE
MEK inhibitor effective against proliferation in breast cancer cell Yan Zhou & Hai-yan Hu & Wei Meng & Ling Jiang & Xing Zhang & Jing-jing Sha & Zhigang Lu & Yang Yao
Received: 26 January 2014 / Accepted: 26 March 2014 # International Society of Oncology and BioMarkers (ISOBM) 2014
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, miR203 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.
Keywords AZD6244 . Breast cancer . miR-203 . CUL1
Yan Zhou and Hai-yan Hu, the first authors, contributed equally to this work. Y. Zhou : H.
RESEARCH ARTICLE
MEK inhibitor effective against proliferation in breast cancer cell Yan Zhou & Hai-yan Hu & Wei Meng & Ling Jiang & Xing Zhang & Jing-jing Sha & Zhigang Lu & Yang Yao
Received: 26 January 2014 / Accepted: 26 March 2014 # International Society of Oncology and BioMarkers (ISOBM) 2014
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, miR203 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.
Keywords AZD6244 . Breast cancer . miR-203 . CUL1
Yan Zhou and Hai-yan Hu, the first authors, contributed equally to this work. Y. Zhou : H.
