MEK inhibitor effective against proliferation in breast cancer cell.

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.
Authors	Yan Zhou, Hai-Yan Hu, Wei Meng, Ling Jiang, Xing Zhang, Jing-Jing Sha, Zhigang Lu, Yang Yao
Journal	Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine (Tumour Biol) Vol. 35 Issue 9 Pg. 9269-79 (Sep 2014) ISSN: 1423-0380 [Electronic] Netherlands
PMID	24938872 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	AZD 6244 Benzimidazoles Cullin 1 Cullin Proteins MIRN203 microRNA, human MicroRNAs Protein Kinase Inhibitors Mitogen-Activated Protein Kinases
Topics	Apoptosis (drug effects) Benzimidazoles (pharmacology) Breast Neoplasms (genetics, metabolism, pathology) Cell Line, Tumor Cell Proliferation (drug effects) Cell Survival (drug effects) Cullin Proteins (genetics, metabolism) Female G1 Phase Cell Cycle Checkpoints (drug effects) Gene Expression Regulation, Neoplastic Humans MicroRNAs (genetics) Mitogen-Activated Protein Kinases (metabolism) Oligonucleotide Array Sequence Analysis Protein Kinase Inhibitors (pharmacology) RNA Interference Reverse Transcriptase Polymerase Chain Reaction Signal Transduction (drug effects) Up-Regulation

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