Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology.
Genes Dev. 2013 Jul 1;27(13):1435-40. doi: 10.1101/gad.220202.113. Epub 2013 Jun 24.
Androgen-deprived prostate cancer (PCa) is infiltrated by B lymphocytes that produce cytokines that activate IκB kinase α (IKKα) to accelerate the emergence of castration-resistant tumors. We now demonstrate that infiltrating B lymphocytes and IKKα are also required for androgen-dependent expansion of epithelial progenitors responsible for prostate regeneration. In these cells and in PCa cells, IKKα phosphorylates transcription factor E2F1 on a site that promotes its nuclear translocation, association with the coactivator CBP, and recruitment to critical genomic targets that include Bmi1, a key regulator of normal and cancerous prostate stem cell renewal. The IKKα-BMI1 pathway is also activated in human PCa.
去雄激素前列腺癌（PCa）被产生细胞因子的 B 淋巴细胞浸润，这些细胞因子激活 IκB 激酶α（IKKα），从而加速去势抵抗性肿瘤的出现。我们现在证明，浸润的 B 淋巴细胞和 IKKα 对于负责前列腺再生的上皮祖细胞的雄激素依赖性扩增也是必需的。在这些细胞和 PCa 细胞中，IKKα 在促进其核易位、与共激活因子 CBP 结合以及募集到包括 Bmi1 在内的关键基因组靶标的位点上磷酸化转录因子 E2F1，Bmi1 是正常和癌性前列腺干细胞更新的关键调节因子。IKKα-BMI1 通路在人类 PCa 中也被激活。
