Role of the TMPRSS2-ERG gene fusion in prostate cancer.
By S. Tomlins, B. Laxman, S. Varambally, Xuhong Cao, Jindan Yu, Beth E. Helgeson, Q. Cao, John R. Prensner, Mark A. Rubin, R. Shah and 2 more. Neoplasia, 2008
715 citations recorded by the source corpus.
TMPRSS2-ERG gene fusions are the predominant molecular subtype of prostate cancer. Here, we explored the role of TMPRSS2-ERG gene fusion product using in vitro and in vivo model systems. Transgenic mice expressing the ERG gene fusion product under androgen-regulation develop mouse prostatic intraepithelial neoplasia (PIN), a precursor lesion of prostate cancer. Introduction of the ERG gene fusion product into primary or immortalized benign prostate epithelial cells induced an invasion-associated transcriptional program but did not increase cellular proliferation or anchorage-independent growth. These results suggest that TMPRSS2-ERG may not be sufficient for transformation in the absence of secondary molecular lesions. Transcriptional profiling of ERG knockdown in the TMPPRSS2-ERG-positive prostate cancer cell line VCaP revealed decreased expression of genes over-expressed in prostate cancer versus PIN and genes overexpressed in ETS-positive versus -negative prostate cancers in addition to inhibiting invasion. ERG knockdown in VCaP cells also induced a transcriptional program consistent with prostate differentiation. Importantly, VCaP cells and benign prostate cells overexpressing ERG directly engage components of the plasminogen activation pathway to mediate cellular invasion, potentially representing a downstream ETS target susceptible to therapeutic intervention. Our results support previous work suggesting that TMPRSS2-ERG fusions mediate invasion, consistent with the defining histologic distinction between PIN and prostate cancer.
Subfields: Molecular Biology, Pulmonary and Respiratory Medicine
View Paper: https://www.semanticscholar.org/paper/68dcb0d8cff852accf1ccca3c7a382c631056cb3
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In Molecular Biology
- Christopher Sander
- Arul M. Chinnaiyan
- B. Reva
- Yevgeniy Antipin
- Nikolaus Schultz
- C. Abate-Shen
- Zhaohui S. Qin
- M. Shen
In Pulmonary and Respiratory Medicine
Citations in the corpus
- Molecular genetics of prostate cancer: new prospects for old challenges. (2010, background): “While evidence of major subtypes of prostate cancer is lacking at the histopathological level, recent genomic analyses have provided increasing evidence for molecularly defined subtypes (Tomlins et al. 2008b; Palanisamy et al. 2010; Taylor et al. 2010).”
- Integrative genomic profiling of human prostate cancer (2010, background): “Functional studies of TMPRSS2-ERG, including transgenic expression in the mouse prostate, have shown modest evidence of oncogenic activity (Carver et al., 2009; King et al., 2009; Klezovitch et al., 2008; Tomlins et al., 2008), which raises the possibility that cooperating events are required.”
- An Integrated Network of Androgen Receptor, Polycomb, and TMPRSS2-ERG Gene Fusions in Prostate Cancer Progression (2010, methodology): “Adenoviral and lentiviral constructs expressing ERG or GUS control were generated as previously described by recombining pCR8ERG and a control entry clone (pENTR-GUS) (Invitrogen) with pAD/CMV/V5 and pLenti6/CMV/V5, respectively, using LR Clonase II (Invitrogen) (Tomlins et al., 2008).”