Mammary-specific ectopic expression of mutant human GATA3 did not potentiate medroxyprogesterone acetate-driven mouse mammary tumorigenesis

Abstract

ABSTRACTGATA3 is somatically mutated in approximately 15% of estrogen receptor positive human breast tumors, however the mechanism(s) by which these alterations contribute to tumorigenesis are unclear. The observed patterns of mutations suggest a strong selective pressure to mutate a single allele of GATA3 in a manner favoring retention of the first of two zinc finger domains. The non-mutated GATA3 allele is maintained and expressed. We and others have hypothesized that expression of the mutant GATA3 protein may actively contribute to breast tumorigenesis, however the aging of several independently generated mouse models with mammary-specific mutant GATA3 expression did not result in tumorigenesis. In this study, we evaluated whether a mammary tumor-promoting dose of medroxyprogesterone acetate could synergize with mammary specific mutant GATA3 (G335fs) expression and accelerate the kinetics of tumor formation. We report that the tumor incidence rate in these animals did not differ from that observed in wild-type littermate controls.