title: Transcriptional repression of AIB1 by FoxG1 leads to apoptosis in breast cancer cells.
abstract: The oncogene nuclear receptor coactivator amplified in breast cancer 1 (AIB1) is a transcriptional coactivator that is overexpressed in various types of human cancers. However, the molecular mechanisms controlling AIB1 expression in the majority of cancers remain unclear. In this study, we identified a novel interacting protein of AIB1, forkhead-box protein G1 (FoxG1), which is an evolutionarily conserved forkhead-box transcriptional corepressor. We show that FoxG1 expression is low in breast cancer cell lines and that low levels of FoxG1 are correlated with a worse prognosis in breast cancer. We also demonstrate that transient overexpression of FoxG1 can suppress endogenous levels of AIB1 mRNA and protein in MCF-7 breast cancer cells. Exogenously expressed FoxG1 in MCF-7 cells also leads to apoptosis that can be rescued in part by AIB1 overexpression. Using chromatin immunoprecipitation, we determined that FoxG1 is recruited to a region of the AIB1 gene promoter previously characterized to be responsible for AIB1-induced, positive autoregulation of transcription through the recruitment of an activating, multiprotein complex, involving AIB1, E2F transcription factor 1, and specificity protein 1. Increased FoxG1 expression significantly reduces the recruitment of AIB1, E2F transcription factor 1 and E1A-binding protein p300 to this region of the endogenous AIB1 gene promoter. Our data imply that FoxG1 can function as a pro-apoptotic factor in part through suppression of AIB1 coactivator transcription complex formation, thereby reducing the expression of the AIB1 oncogene.
authors: Department of Pharmacology, Lombardi Cancer Center, Georgetown University, Research Building E307, 3970 Reservoir Road Northwest, Washington, DC 20007-2197, USA.
authors: Jordan V
authors: JV
authors: Li
authors: Christopher D
authors: CD
authors: Chien
authors: Jason P
authors: JP
authors: Garee
authors: Jianming
authors: J
authors: Xu
authors: Anton
authors: A
authors: Wellstein
authors: Anna T
authors: AT
authors: Riegel
mesh_terms: D017209:Apoptosis / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D015536:Down-Regulation / Q000235:genetics; D050687:E2F1 Transcription Factor / Q000378:metabolism; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D061986:MCF-7 Cells; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D056921:Nuclear Receptor Coactivator 3 / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000235:genetics; D055550:Protein Stability; D012097:Repressor Proteins / Q000378:metabolism*; D016329:Sp1 Transcription Factor / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; C090173:FOXG1 protein, human; D051858:Forkhead Transcription Factors; D009419:Nerve Tissue Proteins; D012097:Repressor Proteins; D016329:Sp1 Transcription Factor; C538866:NCOA3 protein, human; D056921:Nuclear Receptor Coactivator 3
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