The MMTV-Wnt1 murine model produces two phenotypically distinct subtypes of mammary tumors with unique therapeutic responses to an EGFR inhibitor.

摘要: The Wnt gene family encodes an evolutionarily conserved group of proteins that regulate cell growth, differentiation and stem self-renewal. Aberrant signaling in human breast tumors has been proposed as a driver tumorigenesis, especially the basal-like tumor subtype where canonical is both enriched predictive poor clinical outcomes. development effective Wnt-based therapeutics, however, slowed part by limited understanding context-dependent nature with which these aberrations influence tumorigenesis. We previously reported MMTV-Wnt1 mice, established model for studying tumors, develop two subtypes expression classification: Wnt1-EarlyEx Wnt1-LateEx Here, we extend this initial observation show exhibit high Wnt, non-canonical EGFR pathway signatures. Therapeutically, showed dynamic reduction volume when treated inhibitor. had primarily Cd49fpos/Epcamneg FACS profiles, but it was not possible to serially transplant into wild-type FVB female mice. Conversely, bloody gross pathology, highlighted presence 'blood lakes' identified H&E staining. These Cd49fpos/Epcampos also contained secondary subpopulation. were activating Hras1 mutations capable reproducing transplanted This study definitively shows mouse produces phenotypically distinct mammary differ multiple biological aspects including sensitivity