FOXP1 as a Potential ER Coregulator in Human Breast Cancer.

Abstract Estrogen activates the estrogen receptor (ER) by recruiting various coregulators and cofactors, resulting in transcriptional regulation of target genes. Recently, we have shown that the FOXP1 forkhead transcription factor is a novel androgen-regulated coregulator for the androgen receptor (Biochem Biophys Res Commun, 374, 388-93, 2008). However, its role in breast cancer is still unknown.Here, we investigated the expression pattern of FOXP1 by immunohistochemistry in a series of 110 invasive breast cancers and compared it with clinicopathological factors. The expression of FOXP1 was detected in nuclei in 76 cases (69.1%) and correlated with expressions of ERα (P=0.001) and progesterone receptor (PgR) (P=0.003), while there was no association with age, lymph node status, size, or grade. Expression levels of FOXP1 mRNA are investigated by qRT-PCR using samples selectively obtained from breast cancer specimens with laser microdissection system (Zeiss Axiovert + P.A.L.M laser microdisection system). ERα, ERβ, and PgR mRNA levels were also measured.Then, we examined expression and function of FOXP1 in human breast cancer MCF-7 cells that possess functional ERα. The expression level of FOXP1 mRNA was up-regulated by estrogen treatment. In addition, estrogen-responsive element-driven luciferase reporter analysis showed that exogenously transfected FOXP1 increased estrogen-dependent transcriptional activity. We also observed that FOXP1 overexpression and knockdown could modulate the growth of MCF-7 cells.Taken together, these findings suggest that FOXP1 plays an important role as a potential ER coregulator in human breast cancer. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4149.