Expression of ERG protein in prostate cancer: variability and biological correlates.
Expression of ERG protein in prostate cancer: variability and biological correlates.
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DOI：
10.1530/erc-14-0586
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发表时间：
2015-06
影响因子：
3.9
通讯作者：
Ittmann M
中科院分区：
文献类型：
--
作者：
Ayala G;Frolov A;Chatterjee D;He D;Hilsenbeck S;Ittmann M
Prostate cancer is the second leading cause of cancer-related death for men in the United States. The TMPRSS2/ERG (T/E) fusion gene is present in approximately 50% of prostate cancers and promotes tumor progression in vivo. The presence of the T/E fusion gene is strongly associated with ERG protein expression but emerging evidence suggests significant interfocal and intrafocal variability in levels of ERG protein expression. We therefore analyzed ERG protein expression by image analysis to objectively quantitate the extent of such heterogeneity and confirmed significant interfocal and intrafocal variability of ERG protein expression levels in cancer expressing ERG. To define the pathways associated with ERG and its variable expression in prostate cancer we have analyzed correlations of ERG expression, as evaluated by immunohistochemistry, with 46 key proteins associated with signal transduction, transcriptional control and other processes using a large tissue microarray with more than 500 prostate cancers. We found significant correlation of ERG expression with markers of activation of the PI3K, MYC and NFkB pathways, which had previously been linked directly or indirectly to ERG expression. We have also identified significant correlations with novel proteins not previously linked to ERG expression including serum response factor, the p160 coactivator SRC1 and Sprouty1. Of note, SKP2 is only correlated with high level ERG protein expression. Thus ERG expression is variable in prostate cancer and is associated with activation of multiple pathways and proteins including several potentially targetable pathways.
