Forkhead (Fox) proteins are an important class of transcription factors (TFs) that act as molecular “pioneers” by increasing chromatin accessibility. The ability of FoxA1 to act in this manner allows for the subsequent nucleation of responsive promoters by additional, tissue specific TFs, allowing for gene regulation. Our laboratory has previously shown that FoxA1 interacts directly with the androgen receptor (AR), and that the expression of FoxA1 is essential for normal prostate maturation and differentiation. Thus, the ability of FoxA1 to enter a transcriptional complex with AR and other TFs contributes to tissue-specific gene expression in the prostate, and determining the components of FoxA1/AR TF complexes will identify additional targets for the treatment of castrate-resistant PCa.

In order to identify additional proteins that interact with FoxA1, we ectopically expressed dual-affinity tagged FoxA1 in the human PCa cell line LNCaP. Following tandem purification and mass spectrometric analysis, we identified several FoxA1-interacting proteins, including Nuclear Factor I x (NFIx). NFIx is a member of the Nuclear Factor family of TFs, consisting of NFIa, NFIb, NFIc, and NFIx. Co-immunoprecipitation studies verify that NFI family members interact with FoxA1, and Chromatin immunoprecipitation (ChIP) experiments indicate NFI family members bind to androgen regulated, prostate-specific promoters. Finally, transient transfection experiments indicate that NFI family members modulate the androgenic stimulation of the Probasin and PSA promoters both in the presence and absence of FoxA1.

In summary, we have identified NFIx as a novel FoxA1 interacting protein. NFI family members act to modulate the transcriptional activity of FoxA1 and AR on prostate-specific target promoters.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1231.