Monoallelic expression of TMPRSS2/ERG in prostate cancer stem cells

Abstract

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.

Aberrant allele-switch imprinting of a novel IGF1R intragenic antisense non-coding RNA in breast cancers

“…The 'G' allele, however, is rarely used by the host machinery for transcription. Similar cases have been reported in the TMPRSS2 gene in prostate cancer stem cells [42]. In addition, stochastic monoallelic expression is also widespread in mammalian genomes, including olfactory receptor, V1rb2 receptor, T-cell receptor and immunoglobulin genes, pheromone receptors, p120 catenin, odorant receptors, and protocadherins [43][44][45][46][47].…”

miR-25 Modulates Invasiveness and Dissemination of Human Prostate Cancer Cells via Regulation of αv- and α6-Integrin Expression

“…The cellular composition and proportion of a2b1 hi /CD133 þ , a2b1 hi /CD133 À and a2b1 low , also referred to as stem-like cells, TA cells, and CB cells (12) in the normal prostate epithelium versus prostate cancer epithelium is indeed generally very different (5). For instance, the "driver" stem/ progenitor subpopulation in the human prostate often represents only 0.02% of all prostate epithelial cells (5,41). The increase in absolute expression levels of miR-25 in bulk tissues during prostate cancer progression may, therefore, be indicative of an increase in the proportion of more differentiated, less invasive, miR-25 high luminal epithelial cells.…”

Cancer Stem Cells in Prostate Cancer: Implications for Targeted Therapy

“…Polson et al [49] demonstrated the presence and expression of TMPRSS2:ERG in PCSCs, which would provide ERG-driven survival advantages. Moreover, ALDH + PCa cells have been shown to exhibit several CSC characteristics such as clonogenicity, migration, tumorigenicity, and propensity to form metastases in vivo [3,10] .…”