Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA.
Mol Cell. 2009 Nov 13;36(3):405-16. doi: 10.1016/j.molcel.2009.10.020.
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.
HOXB13 是同源盒家族的一员，是一种序列特异性转录因子，与雄激素受体（AR）一起在前列腺正常发育中发挥关键作用。我们在这里证明，在前列腺癌细胞中，HOXB13 是对雄激素反应的关键决定因素。具体而言，已经确定 HOXB13 与 AR 的 DNA 结合域相互作用，并抑制包含雄激素反应元件（ARE）的基因的转录。相比之下，AR:HOXB13 复合物使包含特定 HOXB13 反应元件的启动子具有雄激素反应性。此外，HOXB13 和 AR 协同作用以增强包含 ARE 并列的 HOX 元件的基因的转录。HOXB13 敲低对前列腺癌细胞中雄激素调节的增殖、迁移和脂肪生成的深远影响突出了观察到的基因表达变化的重要性。
