PLZF-Mediated Resistance to ADT

Whole-exome sequencing of metastatic castration-resistant prostate cancer (mCRPC) reveals that 5% to 7% of tumors harbor promyelocytic leukemia zinc finger (PLZF) protein homozygous deletions. PLZF is a canonical androgen-regulated putative tumor suppressor gene whose expression is inhibited by androgen deprivation therapy (ADT). Here, we demonstrate that knockdown of PLZF expression promotes a CRPC and enzalutamide-resistant phenotype in prostate cancer cells. Reintroduction of PLZF expression is sufficient to reverse androgen-independent growth mediated by PLZF depletion. PLZF loss enhances CRPC tumor growth in a xenograft model. Bioinformatic analysis of the PLZF cistrome shows that PLZF negatively regulates multiple pathways, including the MAPK pathway. Accordingly, our data support an oncogenic program activated by ADT. This acquired mechanism together with the finding of genetic loss in CRPC implicates PLZF inactivation as a mechanism promoting ADT resistance and the CRPC phenotype. Cancer Res; 75(10); 1944–8. ©2015 AACR.
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Priority Reports Source Type: research

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Source: Microbial Pathogenesis - Category: Infectious Diseases Source Type: research
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Source: Critical Care Medicine - Category: Emergency Medicine Tags: Online Clinical Investigations Source Type: research
No abstract available
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Source: Critical Care Medicine - Category: Emergency Medicine Tags: Feature Articles Source Type: research
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Source: Biomed Res - Category: Research Authors: Tags: Adv Biomed Res Source Type: research
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Source: The Annals of Thoracic Surgery - Category: Cardiovascular & Thoracic Surgery Source Type: research
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Source: Artificial Cells, Nanomedicine and Biotechnology - Category: Biotechnology Tags: Artif Cells Nanomed Biotechnol Source Type: research
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Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
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