Abstract
HOXB13 is a member of the homeodomain family of sequence-specific transcription factors and, together with the androgen receptor (AR), plays a critical role in the normal development of the prostate gland. We demonstrate here that, in prostate cancer cells, HOXB13 is a key determinant of the response to androgens. Specifically, it was determined that HOXB13 interacts with the DNA-binding domain of AR and inhibits the transcription of genes that contain an androgen-response element (ARE). In contrast, the AR:HOXB13 complex confers androgen responsiveness to promoters that contain a specific HOXB13-response element. Further, HOXB13 and AR synergize to enhance the transcription of genes that contain a HOX element juxtaposed to an ARE. The profound effects of HOXB13 knockdown on androgen-regulated proliferation, migration, and lipogenesis in prostate cancer cells highlight the importance of the observed changes in gene expression.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Amino Acid Sequence
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Blotting, Western
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Cell Line
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Cell Line, Tumor
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Cell Movement / drug effects
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Cell Proliferation / drug effects
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Chromatin Immunoprecipitation
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Cluster Analysis
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism
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Gene Expression Profiling
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Gene Expression Regulation / drug effects
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Green Fluorescent Proteins / genetics
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Green Fluorescent Proteins / metabolism
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Homeodomain Proteins / genetics
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Homeodomain Proteins / metabolism*
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Humans
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Lipid Metabolism / drug effects
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Male
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Metribolone / pharmacology*
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Prostatic Neoplasms / genetics
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Prostatic Neoplasms / metabolism
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Prostatic Neoplasms / pathology
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Protein Binding / drug effects
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RNA, Small Interfering / genetics
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Receptors, Androgen / genetics
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Receptors, Androgen / metabolism*
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Response Elements / genetics
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Reverse Transcriptase Polymerase Chain Reaction
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Transfection
Substances
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AR protein, human
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DNA-Binding Proteins
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HOXB13 protein, human
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Homeodomain Proteins
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RNA, Small Interfering
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Receptors, Androgen
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Recombinant Fusion Proteins
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Green Fluorescent Proteins
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Metribolone