GSE127862 ER α over-expression does not accelerate development of p53-deficient mammary tumors in mice [RNA-Seq]

Contributors : Lisette M Cornelissen ; Linda Henneman ; Anne Paulien Drenth ; Eva Schut ; Roebi de Bruijn ; Wilbert Zwart ; Jos JonkersSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiens ; Mus musculusAbout 75% of all breast cancers express the nuclear hormone receptor oestrogen receptor α (ERα). However, the majority of mammary tumors from genetically engineered mouse models are ERα-negative. To model ERα-positive breast cancer in mice, we exogenously introduced expression of mouse and human ERα in an existing p53-deficiency driven breast cancer mouse model. After initial ERα expression during development of the mammary gland, expression was reduced or lost in adult glands and p53-deficient mammary tumors. ChIP-sequencing analysis of primary mouse mammary epithelial cells (MMECs) derived from these models, in which expression of the ERα constructs was induced in vitro, confirmed interaction of ERα with the DNA. In human breast and endometrial cancer, the pioneer factor FOXA1 is known to be essential to facilitate ERα/DNA binding. Surprisingly, the ERα binding sites identified in primary MMECs, but also in mouse mammary gland and uterus, showed a high enrichmen t of ERE motifs, but were devoid of Forkhead motifs. Furthermore, exogenous introduction of FOXA1 and GATA3 in ERα-expressing MMECs was not sufficient to promote ERα-responsiveness of these cells. Together, this suggests that species-specific differences in ERα-c...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Mus musculus Source Type: research