a1 Departments of Surgery, Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
a2 Department of Pathology and Internal Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Breast cancer is a heterogeneous disease and classification is important for clinical management. At least five subtypes can be identified based on unique gene expression patterns; this subtype classification is distinct from the histopathological classification. The transcription factor network(s) required for the specific gene expression signature in each of these subtypes is currently being elucidated. The transcription factor network composed of the oestrogen (estrogen) receptor α (ERα), FOXA1 and GATA3 may control the gene expression pattern in luminal subtype A breast cancers. Breast cancers that are dependent on this network correspond to well-differentiated and hormone-therapy-responsive tumours with good prognosis. In this review, we discuss the interplay between these transcription factors with a particular emphasis on FOXA1 structure and function, and its ability to control ERα function. Additionally, we discuss modulators of FOXA1 function, ERα–FOXA1–GATA3 downstream targets, and potential therapeutic agents that may increase differentiation through FOXA1.
c1 Corresponding author: Harikrishna Nakshatri, R4-202, Indiana University School of Medicine, 1044 West Walnut Street, Indianapolis, IN 46202, USA. Tel: +1 317 278 2238; Fax: +1 317 274 0396; E-mail: [email protected]