Aberrant ERG expression cooperates with loss of PTEN to promote cancer progression in the prostate

By B. Carver, J. Tran, A. Gopalan, Zhenbang Chen, S. Shaikh, Arkaitz Carracedo, A. Alimonti, C. Nardella, Shohreh Varmeh, P. Scardino and 3 more. Nature Genetics, 2009

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Chromosomal translocations involving the ERG locus are frequent events in human prostate cancer pathogenesis; however, the biological role of aberrant ERG expression is controversial. Here we show that aberrant expression of ERG is a progression event in prostate tumorigenesis. We find that prostate cancer specimens containing the TMPRSS2-ERG rearrangement are significantly enriched for loss of the tumor suppressor PTEN. In concordance with these findings, transgenic overexpression of ERG in mouse prostate tissue promotes marked acceleration and progression of high-grade prostatic intraepithelial neoplasia (HGPIN) to prostatic adenocarcinoma in a Pten heterozygous background. In vitro overexpression of ERG promotes cell migration, a property necessary for tumorigenesis, without affecting proliferation. ADAMTS1 and CXCR4, two candidate genes strongly associated with cell migration, were upregulated in the presence of ERG overexpression. Thus, ERG has a distinct role in prostate cancer progression and cooperates with PTEN haploinsufficiency to promote progression of HGPIN to invasive adenocarcinoma.

Subfields: Immunology and Allergy, Molecular Biology, Pulmonary and Respiratory Medicine

View Paper: https://www.semanticscholar.org/paper/a7b379422470a7839b764f0d2daaf6dd0231d4ff

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In Immunology and Allergy

R. DePinho

In Molecular Biology

In Pulmonary and Respiratory Medicine

Citations in the corpus

Molecular genetics of prostate cancer: new prospects for old challenges. (2010, background): “1 homeobox gene, upregulation of the c-Myc proto-oncogene, or the TMPRSS- ERG fusion (Kim et al. 2002c, 2009; Carver et al. 2009; King et al. 2009).”
PTEN loss in the continuum of common cancers, rare syndromes and mouse models (2011, neutral): “, in mice can cooperate with Pten hemizygosity to accelerate invasive prostate adenocarcinoma”
Genomic correlates of clinical outcome in advanced prostate cancer (2019, background): “Alterations in ERG and PTEN were co-occurring, in line with their synergistic role in promoting oncogenesis in mouse models of prostate cancer (17).”
Identification of multipotent luminal progenitor cells in human prostate organoid cultures (2014, positive): “Organoids derived from PBCre Rosa26 LSL-ERG mice showed no signs of neoplasia (Figures 3A andS3B), consistent with the in vivo phenotype (Carver et al., 2009; Chen et al., 2013).”
Genetics and biology of prostate cancer (2018, background): “Furthermore, ERG overexpression combined with PTEN inactivation exhibits PIN with progression to prostate adenocarcinoma (Carver et al. 2009; King et al. 2009; Linn et al. 2015).”
Integrative genomic profiling of human prostate cancer (2010, background): “ERG in transgenic mice and in a prostate tissue reconstitution model (Carver et al., 2009; King et al., 2009; Zong et al., 2009).”
Subtle variations in Pten dose determine cancer susceptibility (2010, background): “This may be due to the existence of a higher phosphatidylinositol-3-OH kinase (PI3K) signaling threshold, as it is likely specific tissues have differential sensitivity to the output of this signaling pathway, and to the requirement for additional genetic events in causing neoplasia in mice (for exa”
Androgen-induced TOP2B mediated double strand breaks and prostate cancer gene rearrangements (2010, background): “However, if a rare genomic error leading to rearrangement of the TMPRSS2 and ERG loci does occur, then this event is likely to become subject to strong selectio”