Session: SUN 292-302-Breast & Prostate Cancer
Poster Board SUN-297
Methods & Results: Using the model of the Mouse Mammary Tumor Virus (MMTV) promoter-driven transgenic expression of Her2/neu we identified epithelial co-localization of Her2/neu and FGFR2 in resulting adenocarcinomas. We also noted nuclear localization of Her2/neu in breast cancer MCF-7 cells that endogenously express the FGFR2-IIIb splice variant; an effect enhanced by the dedicated FGF ligand FGF7. Knockdown of FGFR2 in these cells was associated with attenuated Her2/neu nuclear translocation. Conversely, retroviral transduction of breast epithelial MCF-10A cells with or without FGFR2-IIIb and Her2/neu corroborated translocation of both oncoproteins from the plasma membrane into the nucleus under FGF7 control. The co-expression FGFR2 and Her2/neu resulted in enhanced STAT3 activation accompanied by EGF-independent cell proliferation. These actions were subject to Lapatinib-mediated pharmacologic inhibition consistent with the kinase requirement of Her2/neu.
Conclusions & Future Prospects: Our studies implicate a novel combination in the ErbB signalling network and demonstrate the synergistic interactions between the FGFR2 and Her2/neu susceptibility gene products in regulating cancer cell behaviour. These data have potentially important therapeutic implications in the development of new targeting strategies for breast and other ErbB-dependent cancers.
Nothing to Disclose: WCW, WL, SLA, SZE
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