184AA3: a xenograft model of ER(+) XXXX .

@entity172 @entity1 @entity0 @entity5 @entity1759 @entity420
UNASSIGNED: Despite the prevalence and  significant morbidity resulting from @entity172 receptor positive (ER(+)) @entity0 , there are only a few models of this @entity5 subtype available for drug development and arguably none for studying etiology. Those models that do exist have questionable clinical relevance. Given our goal of developing luminal models, we focused on six cell lines derived by minimal mutagenesis from normal @entity1 breast cells, and asked if any could generate clinically relevant xenografts, which we then extensively characterized. Xenografts of one cell line, 184AA3, consistently formed ER(+) @entity420 that had a high proliferative rate and other features consistent with "luminal B" intrinsic subtype. Squamous and spindle cell/mesenchymal differentiation was absent, in stark contrast to other cell lines that we examined or others have reported. We explored intratumoral heterogeneity produced by 184AA3 by immunophenotyping xenograft @entity5 and cultured cells, and characterized marker expression by immunofluorescence and flow cytometry. A @entity1759 (High)  subpopulation was discovered, yet their @entity5 forming ability was far less than @entity1759 (Low)  cells. Single cell cloning revealed the phenotypic plasticity of 184AA3, consistent with the intratumoral heterogeneity observed in xenografts. Characterization of ER expression in cultures revealed ER protein and signaling is intact, yet when @entity172 was depleted in culture, and  in vivo, it did not impact cell or @entity5 growth, analogous to therapeutically resistant ER(+)  @entity5 . This model is appropriate for studies of the etiology of ovarian hormone independent @entity420 , for identification of therapeutic targets, predictive testing, and drug development.
