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ERG signaling in prostate cancer is driven through PRMT5-dependent methylation of the Androgen Receptor.

eLife (2016-05-18)
Zineb Mounir, Joshua M Korn, Thomas Westerling, Fallon Lin, Christina A Kirby, Markus Schirle, Gregg McAllister, Greg Hoffman, Nadire Ramadan, Anke Hartung, Yan Feng, David Randal Kipp, Christopher Quinn, Michelle Fodor, Jason Baird, Marie Schoumacher, Ronald Meyer, James Deeds, Gilles Buchwalter, Travis Stams, Nicholas Keen, William R Sellers, Myles Brown, Raymond A Pagliarini
RÉSUMÉ

The TMPRSS2:ERG gene fusion is common in androgen receptor (AR) positive prostate cancers, yet its function remains poorly understood. From a screen for functionally relevant ERG interactors, we identify the arginine methyltransferase PRMT5. ERG recruits PRMT5 to AR-target genes, where PRMT5 methylates AR on arginine 761. This attenuates AR recruitment and transcription of genes expressed in differentiated prostate epithelium. The AR-inhibitory function of PRMT5 is restricted to TMPRSS2:ERG-positive prostate cancer cells. Mutation of this methylation site on AR results in a transcriptionally hyperactive AR, suggesting that the proliferative effects of ERG and PRMT5 are mediated through attenuating AR's ability to induce genes normally involved in lineage differentiation. This provides a rationale for targeting PRMT5 in TMPRSS2:ERG positive prostate cancers. Moreover, methylation of AR at arginine 761 highlights a mechanism for how the ERG oncogene may coax AR towards inducing proliferation versus differentiation.

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Description du produit

Sigma-Aldrich
Anticorps anti-glycéraldéhyde-3-phosphate déshydrogénase, clone 6C5, clone 6C5, Chemicon®, from mouse
Sigma-Aldrich
Monoclonal Anti-PRMT5 antibody produced in mouse, ~2 mg/mL, clone PRMT5-21, purified immunoglobulin, buffered aqueous solution