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The <i>ETS-related gene</i> (<i>ERG</i>) is proto-oncogene that is classified as a member of the <i>ETS</i> 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 <i>ERG</i> can mostly be attributed to the fusion of the <i>ERG</i> and <i>transmembrane serine protease 2</i> (<i>TMPRSS2</i>) genes, and this fusion is estimated to represent about 85% of all gene fusions observed in prostate cancer. Clinically, individuals with <i>ERG</i> 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 <i>ERG</i> plays a central role in PCa progression due to its ability to enhance tumor growth by promoting inflammatory and angiogenic responses. <i>ERG</i> 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.