Author/Authors :
Brenner، نويسنده , , J. Chad and Ateeq، نويسنده , , Bushra and Li، نويسنده , , Yong and Yocum، نويسنده , , Anastasia K. and Cao، نويسنده , , Qi and Asangani، نويسنده , , Irfan A. and Patel، نويسنده , , Sonam and Wang، نويسنده , , Xiaoju and Liang، نويسنده , , Hallie and Yu، نويسنده , , Jindan and Palanisamy، نويسنده , , Nallasivam and Siddiqui، نويسنده , , Javed and Yan، نويسنده , , Wei and Cao، نويسنده , , Xuhong and Mehra، نويسنده , , Rohit and Sabolch، نويسنده , , Aaron and Basrur، نويسنده , , Venkatesha and Lonigro، نويسنده , , Robert J. and Yang، نويسنده , , Jun and Tomlins، نويسنده , , Scott A. and Maher، نويسنده , , Christopher A. and Elenitoba-Johnson، نويسنده , , Kojo S.J. and Hussain، نويسنده , , Maha and Navone، نويسنده , , Nora M. and Pienta، نويسنده , , Kenneth J. and Varambally، نويسنده , , Sooryanarayana and Feng، نويسنده , , Felix Y. and Chinnaiyan، نويسنده , , Arul M.، نويسنده ,
Abstract :
Summary
ent fusions of ETS genes are considered driving mutations in a diverse array of cancers, including Ewingʹs sarcoma, acute myeloid leukemia, and prostate cancer. We investigate the mechanisms by which ETS fusions mediate their effects, and find that the product of the predominant ETS gene fusion, TMPRSS2:ERG, interacts in a DNA-independent manner with the enzyme poly (ADP-ribose) polymerase 1 (PARP1) and the catalytic subunit of DNA protein kinase (DNA-PKcs). ETS gene-mediated transcription and cell invasion require PARP1 and DNA-PKcs expression and activity. Importantly, pharmacological inhibition of PARP1 inhibits ETS-positive, but not ETS-negative, prostate cancer xenograft growth. Finally, overexpression of the TMPRSS2:ERG fusion induces DNA damage, which is potentiated by PARP1 inhibition in a manner similar to that of BRCA1/2 deficiency.
