1. The homeodomain protein HOXB13 regulates the cellular response to androgens.
- Author
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Norris JD, Chang CY, Wittmann BM, Kunder RS, Cui H, Fan D, Joseph JD, and McDonnell DP
- Subjects
- Amino Acid Sequence, Blotting, Western, Cell Line, Cell Line, Tumor, Cell Movement drug effects, Cell Proliferation drug effects, Chromatin Immunoprecipitation, Cluster Analysis, DNA-Binding Proteins genetics, DNA-Binding Proteins metabolism, Gene Expression Profiling, Gene Expression Regulation drug effects, Green Fluorescent Proteins genetics, Green Fluorescent Proteins metabolism, Homeodomain Proteins genetics, Humans, Lipid Metabolism drug effects, Male, Prostatic Neoplasms genetics, Prostatic Neoplasms metabolism, Prostatic Neoplasms pathology, Protein Binding drug effects, RNA, Small Interfering genetics, Receptors, Androgen genetics, Recombinant Fusion Proteins genetics, Recombinant Fusion Proteins metabolism, Response Elements genetics, Reverse Transcriptase Polymerase Chain Reaction, Transfection, Homeodomain Proteins metabolism, Metribolone pharmacology, Receptors, Androgen metabolism
- 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.
- Published
- 2009
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