title: FoxA1 specifies unique androgen and glucocorticoid receptor binding events in prostate cancer cells.
abstract: The forkhead protein FoxA1 has functions other than a pioneer factor, in that its depletion brings about a significant redistribution in the androgen receptor (AR) and glucocorticoid receptor (GR) cistromes. In this study, we found a novel function for FoxA1 in defining the cell-type specificity of AR- and GR-binding events in a distinct fashion, namely, for AR in LNCaP-1F5 cells and for GR in VCaP cells. We also found different, cell-type and receptor-specific compilations of cis-elements enriched adjacent to the AR- and GR-binding sites. The AR pathway is central in prostate cancer biology, but the role of GR is poorly known. We find that AR and GR cistromes and transcription programs exhibit significant overlap, and GR regulates a large number of genes considered to be AR pathway-specific. This raises questions about the role of GR in maintaining the AR pathway under androgen-deprived conditions in castration-resistant prostate cancer patients. However, in the presence of androgen, ligand-occupied GR acts as a partial antiandrogen and attenuates the AR-dependent transcription program. .
authors.affiliation: Institute of Biomedicine and Research Programs Unit, Genome-Scale Biology, Biomedicum Helsinki, University of Helsinki, Finland.
authors.forename: Biswajyoti
authors.initials: B
authors.lastname: Sahu
authors.forename: Marko
authors.initials: M
authors.lastname: Laakso
authors.forename: Päivi
authors.initials: P
authors.lastname: Pihlajamaa
authors.forename: Kristian
authors.initials: K
authors.lastname: Ovaska
authors.forename: Ievgenii
authors.initials: I
authors.lastname: Sinielnikov
authors.forename: Sampsa
authors.initials: S
authors.lastname: Hautaniemi
authors.forename: Olli A
authors.initials: OA
authors.lastname: Jänne
mesh_terms: D002369:Castration; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D005796:Genes; D051541:Hepatocyte Nuclear Factor 3-alpha / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008024:Ligands; D008297:Male; D009928:Organ Specificity; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics
chemical_list: C410798:AR protein, human; C496499:FOXA1 protein, human; D051541:Hepatocyte Nuclear Factor 3-alpha; D008024:Ligands; D011944:Receptors, Androgen; D011965:Receptors, Glucocorticoid