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

Abstract

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.