同源盒蛋白 HOXB13 调节细胞对雄激素的反应。
The homeodomain protein HOXB13 regulates the cellular response to androgens.
机构信息
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA.
出版信息
Mol Cell. 2009 Nov 13;36(3):405-16. doi: 10.1016/j.molcel.2009.10.020.
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.
摘要
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。
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