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RETRACTED ARTICLE: EGFR and MET receptor tyrosine kinase–altered microRNA expression induces tumorigenesis and gefitinib resistance in lung cancers
- Source :
- Nature Medicine. 18:74-82
- Publication Year :
- 2011
- Publisher :
- Springer Science and Business Media LLC, 2011.
-
Abstract
- The involvement of the MET oncogene in de novo and acquired resistance of non-small cell lung cancers (NSCLCs) to tyrosine kinase inhibitors (TKIs) has previously been reported, but the precise mechanism by which MET overexpression contributes to TKI-resistant NSCLC remains unclear. MicroRNAs (miRNAs) negatively regulate gene expression, and their dysregulation has been implicated in tumorigenesis. To understand their role in TKI-resistant NSCLCs, we examined changes in miRNA that are mediated by tyrosine kinase receptors. Here we report that miR-30b, miR-30c, miR-221 and miR-222 are modulated by both epidermal growth factor (EGF) and MET receptors, whereas miR-103 and miR-203 are controlled only by MET. We showed that these miRNAs have important roles in gefitinib-induced apoptosis and epithelial-mesenchymal transition of NSCLC cells in vitro and in vivo by inhibiting the expression of the genes encoding BCL2-like 11 (BIM), apoptotic peptidase activating factor 1 (APAF-1), protein kinase C ɛ (PKC-ɛ) and sarcoma viral oncogene homolog (SRC). These findings suggest that modulation of specific miRNAs may provide a therapeutic approach for the treatment of NSCLCs.
- Subjects :
- 0303 health sciences
General Medicine
Biology
medicine.disease_cause
General Biochemistry, Genetics and Molecular Biology
Receptor tyrosine kinase
respiratory tract diseases
3. Good health
03 medical and health sciences
0302 clinical medicine
Gefitinib
Epidermal growth factor
030220 oncology & carcinogenesis
Cancer research
medicine
biology.protein
Signal transduction
Carcinogenesis
Tyrosine kinase
Protein kinase C
030304 developmental biology
Proto-oncogene tyrosine-protein kinase Src
medicine.drug
Subjects
Details
- ISSN :
- 1546170X and 10788956
- Volume :
- 18
- Database :
- OpenAIRE
- Journal :
- Nature Medicine
- Accession number :
- edsair.doi...........b92f2567161e989411c5bf4c6273de67