1] Department of Biomedical Science, University of Sheffield, Firth Court, Western Bank, Sheffield, S10 2TN, UK [2].
Sci Rep. 2013 Sep 30;3:2792. doi: 10.1038/srep02792.
Dystroglycan is frequently lost in adenocarcinoma, but the mechanisms and consequences are poorly understood. We report an analysis of β-dystroglycan in prostate cancer in human tissue samples and in LNCaP cells in vitro. There is progressive loss of β-dystroglycan immunoreactivity from basal and lateral surfaces of prostate epithelia which correlates significantly with increasing Gleason grade. In about half of matched bone metastases there is significant dystroglycan re-expression. In tumour tissue and in LNCaP cells there is also a tyrosine phosphorylation-dependent translocation of β-dystroglycan to the nucleus. Analysis of gene expression data by microarray, reveals that nuclear targeting of β-dystroglycan in LNCaP cells alters the transcription of relatively few genes, the most unregulated being the transcription factor ETV1. These data suggest that proteolysis, tyrosine phosphorylation and translocation of dystroglycan to the nucleus resulting in altered gene transcription could be important mechanisms in the progression of prostate cancer.
肌联蛋白在腺癌中经常丢失，但机制和后果知之甚少。我们报告了对人组织样本和体外 LNCaP 细胞中前列腺癌中β-肌联蛋白的分析。β-肌联蛋白免疫反应性从前列腺上皮的基底和侧面逐渐丢失，与 Gleason 分级的增加显著相关。在大约一半的匹配骨转移中，肌联蛋白的表达显著重新表达。在肿瘤组织和 LNCaP 细胞中，β-肌联蛋白也依赖于酪氨酸磷酸化而向核内易位。通过微阵列分析基因表达数据显示，LNCaP 细胞中β-肌联蛋白的核靶向改变了相对较少基因的转录，最不受调节的是转录因子 ETV1。这些数据表明，肌联蛋白的蛋白水解、酪氨酸磷酸化和向核内易位导致转录基因的改变，可能是前列腺癌进展的重要机制。
