YCR Cancer Research Unit, Department of Biology, University of York, York, North Yorkshire, UK.
Nat Commun. 2013;4:1623. doi: 10.1038/ncomms2627.
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.
虽然染色体易位在几种人类白血病的发展中起着根本作用，但它们在实体瘤发展中的作用有些争议。最近表明，高达 80%的前列腺肿瘤至少携带一种这样的基因融合，并且最常见的融合事件是前列腺特异性 TMPRSS2 基因和 ERG 癌基因之间的融合，这是前列腺癌发展的关键因素，可能是早期因素。在这里，我们证明了这种重要的染色体重排在前列腺癌干细胞中的存在和表达。此外，我们还表明，在来自正常和肿瘤组织的前列腺上皮细胞层次中，TMPRSS2 转录受到严格的单等位基因调控，这种调控在不对称分裂时保留，在上皮细胞分化时放松。前列腺干细胞中 TMPRSS2/ERG 的存在和表达将为 ERG 驱动的生存优势提供保障，从而维持这种突变基因型。
