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MINI 34 - RNA and miRNA (ID 162)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
MINI34.06 - MicroRNA 10b, 27a and 27b Are Upregulated in Lung Cancer Cell with Epidermal Growth Factor (EGFR) Mutation Resistant to EGFR TKI (ID 2950)
18:30 - 20:00 | Author(s): J. Kevern
EGFR Tyrosine Kinase Inhibitor (TKI) is now standard of care in lung cancer patients with EGFR mutation. Invariably, these patients develop resistance and would require treatment with another EGFR TKI or chemotherapy. The gate keeper mutation T790M is responsible for about 50% of resistance cases. There are other mechanisms that could confer resistance in these patients. High expression of microRNA (mir) 10 is associated with worse prognosis in resected lung cancer patients with EGFR mutation. The mir 27a and 27b is associated with increased expression of c-met which is a potential mechanism of resistance to EGFR. We explored the expression of mir 10b and 27a and 27b in lung cancer cell lines with EGFR mutation that were resistant to Erlotinib.
Lung cancer cell lines with EGFR mutation CRL-2868 and CRL 2871 were treated with 5 nM of erlotinib for 24hours and 72 hours. The erlotinib resistant cells were then harvested and then microRNA profiling was done by real time PCR. HTB177 cell line without EGFR mutation was used as control.
We observed an increased expression of mir 10b, mir27a and mir27b in CRL-2871 compared to control HTB 177 cells. Mir 27b is upregulated in both cell lines. The increase expression of mir 10b and mir 27a were higher in CRL-2871 than the control cells 9 fold and 8 folds respectively. The mir 27b was increased 300 folds in the CRL 2868 compared with control.
We observed upregulation of mir 10b, 27a and 27b in lung cancer cells lines with EGFR mutation that were resistant to Erlotinib treatment. This suggests an epigenetic mechanism of resistance other than the T790M mutation. Further research in patients with EGFR mutation resistance to EGFR TKI should be done to confirm this finding.