Nemo-like kinase induces apoptosis and inhibits androgen receptor signaling in prostate cancer cells.
Nemo-like kinase induces apoptosis and inhibits androgen receptor signaling in prostate cancer cells.
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DOI：
10.1002/pros.20998
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发表时间：
2009-10-01
期刊：
影响因子：
2.8
通讯作者：
Corey, Eva
中科院分区：
文献类型：
--
作者：
Emami, Katayoon H.;Brown, Lisha G.;Pitts, Tiffany E. M.;Sun, Xizhang;Vessella, Robert L.;Corey, Eva
丝裂原激活蛋白激酶 (MAPK) 调节细胞生长、分化和应激反应，许多关键信号传导途径受到 MAPK 信号传导的交叉调节。先前的研究已经提供了 MAPK 通路和雄激素受体 (AR) 信号之间的串扰证据，这在正常前列腺和前列腺癌 (PCa) 的生长控制中发挥着关键作用。本研究的目的是评估 PCa 中 MAPK 样蛋白 nemo 样激酶 (NLK) 的表达及其对 AR 介导的转录的影响。使用实时 PCR 和 IHC 评估前列腺样本中 NLK 的水平。使用蛋白质印迹和流式细胞术测定NLK过度表达对细胞凋亡和增殖的影响。通过 PCa 细胞中 NLK 的过度表达和敲低，并结合 PCR、Western blotting 和报告基因检测来评估对 AR 信号传导的影响。我们的结果表明，与正常前列腺上皮和原发性 PCa 相比，PCa 转移瘤中 NLK 的表达降低。我们的结果还表明，NLK 的过度表达会导致细胞凋亡的诱导，这在表达 AR 的 LNCaP 细胞中比 AR 阴性 PC-3 细胞中更为明显。较高水平的 NLK 会降低 AR mRNA 和蛋白质的水平，并抑制 AR 介导的转录。 NLK 表达在 PCa 进展过程中发生改变，并且参与这些细胞中 AR 信号传导的调节。更深入地了解 NLK 在 AR 介导的转录调节和 PCa 进展控制中的作用可能会为这种疾病的治疗干预新模式指明道路。前列腺 69：1481–1492，2009。
The mitogen-activated protein kinases (MAPKs) regulate cell growth, differentiation, and stress responses, and many critical signaling pathways are subject to cross-regulation by MAPK signaling. Previous studies have yielded evidence of cross-talk between the MAPK pathways and androgen receptor (AR) signaling, which plays a critical role in growth control of both normal prostate and prostate cancer (PCa). Objective of this study was to evaluate the expression of MAPK-like protein nemo-like kinase (NLK) in PCa and its effects on AR-mediated transcription. Real-time PCR and IHC were used to evaluate levels of NLK in prostatic samples. Effects of over-expression of NLK on apoptosis and proliferation were determined using Western blot and flow cytometry. Effects on AR signaling were evaluated using over-expression and knockdown of NLK in PCa cells in combination with PCR, Western blotting and reporter assays. Our results show that the expression of NLK is decreased in PCa metastases in comparison to normal prostate epithelium and primary PCa. Our results also show that over-expression of NLK resulted in induction of apoptosis, which was more pronounced in AR-expressing LNCaP versus AR-negative PC-3 cells. Higher levels of NLK decreased levels of AR mRNA and protein as well as inhibited AR-mediated transcription. NLK expression is altered during PCa progression and it is involved in regulation of AR signaling in these cells. A deeper understanding of the roles of NLK in regulation of AR-mediated transcription and control of PCa progression may point the way to new modes of therapeutic intervention in this disease. Prostate 69: 1481–1492, 2009.
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影响因子：
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Chatterjee, B
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Chatterjee, B
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