The homeodomain protein HOXB13 regulates the cellular response to androgens.
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.
Norris
John D
JD
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA.
Chang
Ching-Yi
CY
Wittmann
Bryan M
BM
Kunder
Rebecca S
RS
Cui
Huaxia
H
Fan
Daju
D
Joseph
James D
JD
McDonnell
Donald P
DP
D000595:Amino Acid Sequence; D015153:Blotting, Western; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D047369:Chromatin Immunoprecipitation; D016000:Cluster Analysis; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D015741:Metribolone / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011485:Protein Binding / Q000187:drug effects; D034741:RNA, Small Interfering / Q000235:genetics; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D020218:Response Elements / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
C410798:AR protein, human; D004268:DNA-Binding Proteins; C484414:HOXB13 protein, human; D018398:Homeodomain Proteins; D034741:RNA, Small Interfering; D011944:Receptors, Androgen; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D015741:Metribolone