Expression of the forkhead transcription factor FOXP1 is associated with that of estrogen receptor beta in primary invasive breast carcinomas

We previously identified a correlation between estrogen receptor alpha (ER alpha) and the candidate tumour suppressor gene Forkhead Box P1 (FOXP1), whose nuclear protein expression in breast tumours was associated with improved patient survival. However, the expression pattern of FOXP1 in normal breast tissue is more reminiscent of the second receptor, ER beta, which has an emerging role as a tumour suppressor in breast cancer and critically may underlie the ability of some ER alpha-negative tumours to respond to tamoxifen. In a series of 283 breast cancers, in which ER alpha-positive tumours were treated with tamoxifen, the nuclear expression of ER beta correlated significantly with ER alpha (p = 0.004), low-tumour grade (p = 0.008) and nuclear FOXP1 (p = 0.01). High-grade tumours exhibited significantly more cytoplasmic ER beta than the low-grade tumours (p = 0.006). Regression analysis demonstrated that FOXP1 expression was most closely related to nuclear ER beta (p = 0.021). Neither, nuclear or cytoplasmic ER beta expression demonstrated prognostic significance. FOXP1 is not estrogen regulated and silencing FOXP1 expression, using siRNA, did not affect ER alpha, ER beta or progesterone receptor expression, suggesting ER and FOXP1 co-expression may reflect a common regulatory mechanism.