Abstract
Traditional treatments for non-small cell lung adenocarcinomas do produce impressive improvements in patient health. Newly developed biologically based treatments exploit the drug-sensitivity conferred by mutations in the epidermal growth factor receptor (EGFR). In adenocarcinomas, cell proliferation and survival depend on mutant EGFR activity. For patients with certain EGFR mutations, treatment with tyrosine kinase inhibitors (TKIs) rather than chemotherapy improves patient survival. However, almost every patient acquires resistance to TKI treatment. About 50% of acquired resistance is because of a secondary mutation in EGFR. MET gene amplification, which allows cells to use MET to activate downstream signals, is another established mechanism. A third known mechanism is epithelial to mesenchymal transition (EMT). About 30% of all resistance mechanisms still remain unknown. This semester, the HCC2279 EGFR-mutant human adenocarcinoma line was characterized in hopes of discovering new models of resistance. Growth inhibition assays and immunoblotting were used to analyze the effects of treatments and to examine the status of signaling molecules. The HCC2279 resistant line appeared to have an EGFR-independent mechanism and did not seem to use MET as a major mechanism of resistance. The resistant cells continued to grow in the presence of TKI and TKI plus MET inhibitor, and immunoblotting showed that TKIs were capable of completely inhibiting the activation and phosphorylation of EGFR and MET. Signs of EMT were detected via immunoblotting due to a loss of E-cadherin and gain of vimentin, and EMT was corroborated by histological changes such as a loss in resistant cell polarity.Copyright for articles published in this journal is retained by the authors, with first publication rights granted to Vanderbilt Undergraduate Research Journal under a Creative Commons Attribution-Noncommercial-ShareAlike 4.0 International License (linked here). By virtue of their appearance in this open access journal, articles are available for wide dissemination at no cost to readers, with proper attribution (acknowledgment of the work's authorship and initial publication in this journal), in educational and other non-commercial settings. Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process.
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