Characterization of stage-specific tumor progression in TMPRSS2-ERG (fusion)-driven and non-fusion-driven prostate cancer in GEM models Journal Article


Authors: Raina, K.; Kant, R.; Prasad, R. R.; Kandhari, K.; Tomar, M.; Mishra, N.; Kumar, R.; Fox, J. T.; Sei, S.; Shoemaker, R. H.; Chen, Y.; Maroni, P.; Agarwal, C.; Agarwal, R.
Article Title: Characterization of stage-specific tumor progression in TMPRSS2-ERG (fusion)-driven and non-fusion-driven prostate cancer in GEM models
Abstract: In the present study, we performed a comparative stage-specific pathological and molecular marker evaluation of TMPRSS2-ERG fusion and PTEN loss-driven (TMPRSS2-ERG. Ptenflox/flox) versus non-fusion-driven prostate tumorigenesis (Hi-Myc) in mice. Anterior, ventral, and dorsolateral prostates were collected from mice at different ages (or time points post-Cre induction). Results indicated that growth and progression of prostatic intraepithelial lesions to adenocarcinoma stages occurred in both mice models albeit at different rates. In the TMPRSS2-ERG. Ptenflox/flox mice, the initiation of tumorigenesis was slow, but subsequent progression through different stages became increasingly faster. Adenocarcinoma stage was reached early on; however, no high-grade undifferentiated tumors were observed. Conversely, in the Hi-Myc+/− mice, tumorigenesis initiation was rapid; however, progression through different stages was relatively slower and it took a while to reach the more aggressive phenotype stage. Nevertheless, at the advanced stages in the Hi-Myc+/− mice, high-grade undifferentiated tumors were observed compared to the later stage tumors observed in the fusion-driven TMPRSS2-ERG. Ptenflox/flox mice. These results were corroborated by the stage specific-pattern in the molecular expression of proliferation markers (PCNA and c-Myc); androgen receptor (AR); fusion-resultant overexpression of ERG; Prostein (SLC45-A3); and angiogenesis marker (CD-31). Importantly, there was a significant increase in immune cell infiltrations, which increased with the stage of tumorigenesis, in the TMPRSS2-ERG fusion-positive tumors relative to fusion negative tumors. Together, these findings are both novel and highly significant in establishing a working preclinical model for evaluating the efficacy of interventions during different stages of tumorigenesis in TMPRSS2-ERG fusion-driven PCa. © 2022 Wiley Periodicals LLC.
Keywords: oncoprotein; genetics; adenocarcinoma; mouse; animal; metabolism; animals; mice; pathology; carcinogenesis; prostate cancer; prostatic neoplasms; prostate; serine proteinase; serine endopeptidases; prostate tumor; transcription factor erg; oncogene proteins, fusion; prostatic intraepithelial neoplasia; erg; tmprss2-erg fusion; humans; human; male; erg protein, human; transcriptional regulator erg; tmprss2 protein, human; hi-myc mice; tmprss2-erg fusion protein, human
Journal Title: Molecular Carcinogenesis
Volume: 61
Issue: 7
ISSN: 0899-1987
Publisher: Wiley Blackwell  
Date Published: 2022-07-01
Start Page: 717
End Page: 734
Language: English
DOI: 10.1002/mc.23413
PUBMED: 35452553
PROVIDER: scopus
PMCID: PMC10007524
DOI/URL:
Notes: Article -- Export Date: 1 July 2022 -- Source: Scopus
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  1. Yu Chen
    134 Chen