PURPOSE: Activating mutations in EGFR promote lung adenocarcinomas. Cyclooxygenase-2 (COX-2) is a cancer target that is commonly overexpressed in solid tumors including lung adenocarcinomas. We hypothesized that COX-2 might be expressed at high levels in lung tumors with activating EGFR mutations.
METHODS: We used mice with an inducible L858R EGFR transgene, which causes them to develop lung adenocarcinomas. By western blotting and immunohistochemistry, we assayed for COX-2 and membrane associated prostaglandin E synthase-1 (mPGES-1), an enzyme that partners with COX-2 to generate prostaglandin E2. We also examined lung cancer cell lines for induction of COX-2 and mPGES-1 upon activation of EGFR.
RESULTS: We found high levels of COX-2 in lungs of L858R EGFR mice compared to control mice. mPGES-1 was also expressed at high levels. In lung cancer cell lines, EGFR ligands induced expression of both COX-2 and mPGES-1.
CONCLUSIONS: COX-2 and mPGES-1 are expressed at high levels in lung tumors of mice with activating mutations in EGFR and both enzymes are induced upon activation of EGFR.
CLINICAL IMPLICATIONS: Both COX-2 and mPGES-1 have tumor promoting properties. Our results suggest that these prostaglandin synthesizing enzymes might have important roles in lung cancer with activating EGFR mutations.
DISCLOSURE: The following authors have nothing to disclose: Roopika Reddy, Yasukazu Hozumi, Matthew Topham
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