Altered endosome biogenesis in prostate cancer has biomarker potential.
Altered endosome biogenesis in prostate cancer has biomarker potential.
复制标题
前列腺癌中内体生物发生的改变具有生物标志物潜力。
DOI：
10.1158/1541-7786.mcr-14-0074
复制
发表时间：
2014-12
期刊：
影响因子：
--
通讯作者：
Brooks DA
中科院分区：
文献类型：
--
作者：
Johnson IR;Parkinson-Lawrence EJ;Shandala T;Weigert R;Butler LM;Brooks DA
前列腺癌是男性中第二常见的癌症，到 70 岁时，八分之一的男性都会受到影响。目前前列腺癌的诊断测试存在假阴性和假阳性的严重问题，因此需要寻找新的分子标记。最近对内体和溶酶体蛋白的研究表明，内体生物发生的关键过程可能在前列腺癌中发生改变。在这里，在前列腺癌和非恶性细胞中评估了一组内体标记物，发现早期内体蛋白质的基因和蛋白质表达显着增加，但晚期内体蛋白质没有显着增加。前列腺癌细胞中早期内体的分布也存在差异，内体运输和转铁蛋白受体（TFRC 和 TFR2）信号传导也发生了改变。这些发现支持前列腺癌中内体生物发生和功能发生改变的概念。临床队列的微阵列分析证实了在培养的前列腺癌细胞中观察到的内体基因表达的改变。此外，在前列腺癌患者组织样本中，早期内体标记物和接头蛋白 APPL1 显示肿瘤附近基底膜组织学的持续改变以及肿瘤块内的集中染色。这些关于改变的早期内体生物发生的新观察为前列腺癌生物标志物研究提供了新途径，并为前列腺癌的早期诊断和准确预后提出了新方法。
Prostate cancer is the second most common form of cancer in males, affecting one in eight men by the time they reach the age of 70. Current diagnostic tests for prostate cancer have significant problems with both false negatives and false positives, necessitating the search for new molecular markers. A recent investigation of endosomal and lysosomal proteins revealed that the critical process of endosomal biogenesis might be altered in prostate cancer. Here, a panel of endosomal markers was evaluated in prostate cancer and non-malignant cells and a significant increase in gene and protein expression was found for early, but not late endosomal proteins. There was also a differential distribution of early endosomes, and altered endosomal traffic and signalling of the transferrin receptors (TFRC and TFR2) in prostate cancer cells. These findings support the concept that endosome biogenesis and function is altered in prostate cancer. Microarray analysis of a clinical cohort confirmed the altered endosomal gene expression observed in cultured prostate cancer cells. Furthermore, in prostate cancer patient tissue specimens, the early endosomal marker and adaptor protein APPL1 showed consistently altered basement membrane histology in the vicinity of tumours and concentrated staining within tumour masses. These novel observations on altered early endosome biogenesis provide a new avenue for prostate cancer biomarker investigation and suggest new methods for the early diagnosis and accurate prognosis of prostate cancer.