| Literature DB >> 21575865 |
J Chad Brenner1, Bushra Ateeq, Yong Li, Anastasia K Yocum, Qi Cao, Irfan A Asangani, Sonam Patel, Xiaoju Wang, Hallie Liang, Jindan Yu, Nallasivam Palanisamy, Javed Siddiqui, Wei Yan, Xuhong Cao, Rohit Mehra, Aaron Sabolch, Venkatesha Basrur, Robert J Lonigro, Jun Yang, Scott A Tomlins, Christopher A Maher, Kojo S J Elenitoba-Johnson, Maha Hussain, Nora M Navone, Kenneth J Pienta, Sooryanarayana Varambally, Felix Y Feng, Arul M Chinnaiyan.
Abstract
Recurrent fusions of ETS genes are considered driving mutations in a diverse array of cancers, including Ewing's 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.Entities:
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Year: 2011 PMID： 21575865 PMCID： PMC3113473 DOI： 10.1016/j.ccr.2011.04.010
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743