Reduced GATA3 expression during breast cancer progression: A potential anchor for pulmonary metastatic deposition

Estrogen receptor (ER) is a direct and reciprocal target gene for GATA3. Previous studies have shown that higher GATA3 expression in primary breast cancer (BC) is associated with a reduced probability of developing lung metastasis when compared to those with metastatic recurrence to other organs. Further, GATA3 downregulates several genes promoting BC lung metastasis and upregulates genes encoding known inhibitors of lung metastasis. In this study, we examined GATA3 expression in 34 consutive cases of paired primary BCs and their pulmonary metastases. Variable levels of GATA3 expression were seen in 94 % primary BCs (mean H-score 239), whereas a significantly reduced GATA3 expression was seen in the paired lung metastases (mean H-score 152; P < 0.0001). However, this trend was not observed for ER (mean H-score 140 vs. 109; P = 0.1). These findings provide further evidence that GATA3 may inhibit pulmonary deposition or sondary growth of BC cells in the lung. The effect of GATA3 in metastatic tumor growth was independent of cell differentiation, and this process is likely mediated by a GATA3-regulated genetic program driven by metastasis-associated genes rather than ER. Further exploring the molecular pathways by which GATA3 regulates downstream targets is pivotal in understanding organ-specific BC dissemination.