[PDF][PDF] The homeodomain protein HOXB13 regulates the cellular response to androgens

JD Norris, CY Chang, BM Wittmann, RS Kunder, H Cui… - Molecular cell, 2009 - cell.com
JD Norris, CY Chang, BM Wittmann, RS Kunder, H Cui, D Fan, JD Joseph, DP McDonnell
Molecular cell, 2009cell.com
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 …
Summary
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.
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