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The Expression of Proto-Oncogene ETS-Related Gene (ERG) Plays a Central Role in the Oncogenic Mechanism Involved in the Development and Progression of Prostate Cancer

Journal

Publisher

MDPI
DOI: 10.3390/ijms23094772

Keywords

ETS-related gene (ERG); TMPRSS2-ERG gene fusion; prostate cancer; tumorigenesis

Funding

  1. Prostate Cancer Foundation USA
  2. Prostate Cancer Canada Movember Award [TAG 2018-2060]

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The ERG gene is consistently overexpressed in prostate cancer and is mainly due to the fusion of ERG and TMPRSS2 genes. ERG enhances tumor growth by promoting inflammatory and angiogenic responses and is involved in the epithelial-mesenchymal transition, increasing the metastatic ability of prostate cancer.
The ETS-related gene (ERG) is proto-oncogene that is classified as a member of the ETS transcription factor family, which has been found to be consistently overexpressed in about half of the patients with clinically significant prostate cancer (PCa). The overexpression of ERG can mostly be attributed to the fusion of the ERG and transmembrane serine protease 2 (TMPRSS2) genes, and this fusion is estimated to represent about 85% of all gene fusions observed in prostate cancer. Clinically, individuals with ERG gene fusion are mostly documented to have advanced tumor stages, increased mortality, and higher rates of metastasis in non-surgical cohorts. In the current review, we elucidate ERG's molecular interaction with downstream genes and the pathways associated with PCa. Studies have documented that ERG plays a central role in PCa progression due to its ability to enhance tumor growth by promoting inflammatory and angiogenic responses. ERG has also been implicated in the epithelial-mesenchymal transition (EMT) in PCa cells, which increases the ability of cancer cells to metastasize. In vivo, research has demonstrated that higher levels of ERG expression are involved with nuclear pleomorphism that prompts hyperplasia and the loss of cell polarity.

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