Monoallelic expression of TMPRSS2/ERG in prostate cancer stem cells

被引：36
作者：
Polson, Euan S. [1 ]
Lewis, John L. [1 ]
Celik, Hamza [2 ]
Mann, Vincent M. [3 ]
Stower, Michael J. [4 ]
Simms, Matthew S. [3 ,5 ]
Rodrigues, Greta [6 ]
Collins, Anne T. [1 ]
Maitland, Norman J. [1 ]
机构：
[1] Univ York, Dept Biol, YCR Canc Res Unit, York YO10 5DD, N Yorkshire, England
[2] Aix Marseille Univ, CNRS, UMR7283, Chim Bacterienne Lab, F-13009 Marseille, France
[3] Univ Hull, Hull York Med Sch, Kingston Upon Hull HU6 7RX, N Humberside, England
[4] York Dist Gen Hosp, York YO31 8HE, N Yorkshire, England
[5] Castle Hill Hosp, Dept Urol, Cottingham HU16 5JQ, Humberside, England
[6] Hull Royal Infirm, Dept Pathol, Kingston Upon Hull HU3 2JZ, N Humberside, England
来源：
NATURE COMMUNICATIONS | 2013年 / 4卷
关键词：
FUSION; ERG; ANDROGEN; IDENTIFICATION; MARKER; CD133;
D O I：
10.1038/ncomms2627
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
While chromosomal translocations have a fundamental role in the development of several human leukaemias, their role in solid tumour development has been somewhat more controversial. Recently, it was shown that up to 80% of prostate tumours harbour at least one such gene fusion, and that the most common fusion event, between the prostate-specific TMPRSS2 gene and the ERG oncogene, is a critical, and probably early factor in prostate cancer development. Here we demonstrate the presence and expression of this significant chromosomal rearrangement in prostate cancer stem cells. Moreover, we show that in the prostate epithelial hierarchy from both normal and tumour tissues, TMPRSS2 transcription is subjected to tight monoallelic regulation, which is retained upon asymmetric division and relaxed during epithelial cell differentiation. The presence and expression of TMPRSS2/ERG in prostate stem cells would provide ERG-driven survival advantages, allowing maintenance of this mutated genotype.
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页数：9
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