P44 Expression of calcium/calcineurin pathway-regulated transcription factor NFATc1 and chromatin-remodelling genes BRG1 and BRM in invasive breast cancer

Abstract

Background: NFATc1 is a transcription factor activated by the calcium/calcineurin pathway, which regulates several physiological processes. Evidence has also shown a role for NFAT transcriptions factors in oncogenesis. BRG1 and BRM are chromatinremodelling genes that are also regulated by calcium homoeostasis. Diminished expression of BRG1 is associated with poor prognosis in breast cancer, non-small-cell lung cancer, colorectal cancer, and prostate cancer. To understand the biological relationship between these two pathways, we examined the expression pattern of NFATc1, BRG1, and BRM in invasive breast cancer. Methods: Paraffin blocks of 150 cases of invasive breast cancer were retrieved from Kaiser Permanente Medical Centre database. Monoclonal antibodies against NFATc1, BRG1, and BRM were used, and expression pattern was determined as no expression, weak (1+ staining intensity), moderate (2+), and high expression (3+). Pearson Chi-Squared test was used for statistical analysis. Findings: NFATc1 was expressed in approximately 22% of the 150 cases of invasive breast cancer, whereas BRG1 was expressed in 56.7% and BRM in 52%. Both nuclear and cytoplasmic expression of NFATc1 was detected, with nuclear expression as the predominant feature. BRM1/BRM are predominantly expressed in the nucleus. Most cases expressing NFATc1 showed 2+ moderate intensity expression patterns. Statistical analysis showed that expression of NFATc1 was highly correlated with the expression of both BRG1 and BRM. Interpretation: Our preliminary data shows that NFATc1 is expressed in a subset of BRG1/BRM-positive invasive breast cancers. This correlation of two calcium homoeostasis-regulated pathways provides insight into the oncogenesis of breast cancer. Funding: Kaiser Hospital Foundation Community Benefit Grant. The author declared no conflicts of interest.