PPARγ and ER pathways have opposite effects onPI3K/AKT signaling that may also account for the inhibitory action of PPARγ ligands on ER-dependent breast cancer cells [36] (see Figure 1).These findings imply that PPARγ antagonism should upregulate ER expression inresponsive tissues, which is precisely the phenotype observed in mammary tumorsinduced in transgenic mice expressing Pax8PPARγ [24]. This evidence concerns the gene ESR1 and breast cancer.