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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.

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