The oncogenic transcription factor ERG represses the transcription of the tumour suppressor gene PTEN in prostate cancer cells
Oncology Letters, accepted ref OL-8815-E151357 (2017) -
Authors: Adamo P, Porazinski P, Rajatileka S, Jumbe S, Hagen R, Cheung M-K, Wilson I, Ladomery M
The oncogene ERG (ETS-related gene) encodes a transcription factor with roles in the regulation of haematopoiesis, angiogenesis, vasculogenesis, inflammation, migration and invasion. The ERG oncogene is activated in over 50% of prostate cancer cases, generally through a gene fusion with the androgen-responsive promoter of TMPRSS2. PTEN (phosphatase and tensin homologue) is an important tumour suppressor gene that is often inactivated in cancer. ERG over expression combined with PTEN inactivation or loss is often associated with aggressive prostate cancer. This study aimed to determine whether or not ERG regulates PTEN transcription directly. ERG was shown to bind to the PTEN promoter and repress its transcription. ERG overexpression reduced endogenous PTEN expression whereas ERG knockdown increased PTEN transcription. The ability of ERG to repress PTEN may contribute to a more cancer-permissive environment.