NRIP1 is activated by C-JUN/C-FOS and activates the expression of PGR , ESR1 and CCND1 in luminal A breast cancer

Using chip array assays, we identified differentially expressed genes via a comparison between luminal A breast cancer subtype and normal mammary ductal cells from healthy donors. In silico analysis confirmed by western blot and immunohistochemistry revealed that C-JUN and C-FOS transcription factors are activated in luminal A patients as potential upstream regulators of these differentially expressed genes. Using a chip-on-chip assay, we identified potential C-JUN and C-FOS targets. Among these genes, the NRIP1 gene was revealed to be targeted by C-JUN and C-FOS. This was confirmed after identification and validation with transfection assays specific binding of C-JUN and C-FOS at consensus binding sites. NRIP1 is not only upregulated in luminal A patients and cell lines but also regulates breast cancer-related genes, including PR , ESR1 and CCND1. These results were confirmed by NRIP1 siRNA knockdown and chip array assays, thus highlighting the putative role of NRIP1 in PGR , ESR1 and CCND1 transcriptional regulation and suggesting that NRIP1 could play an important role in breast cancer ductal cell initiation.