Fig. 3
From: Oncogenic fusion proteins adopt the insulin-like growth factor signaling pathway
Model for TMPRSS2-ERG regulation of the IGF1R gene. Schematic representation of the activation of the IGF1R gene by oncogenic ERG. In prostate cancer cells expressing the chimera, androgens, acting via the androgen receptor (AR), promote transcription of the ERG oncogene. Androgen-stimulated ERG expression results from the fusion of ERG to the androgen sensitive TMPRSS2 promoter. Subsequently, ERG accumulates and transactivates the IGF1R promoter either directly or through complex protein-protein interactions with a series of DNA-binding proteins. Enhanced IGF1R gene expression leads to high levels of expression of the receptor at the cell surface, with ensuing activation by locally produced or circulating IGF1 and/or IGF2. IGF1R overexpression is a typical feature of most cancers and transformed cell lines