A positive role of c-Myc in regulating androgen receptor and its splice variants in prostate cancer

Oncogene
Shanshan BaiYan Dong

Abstract

Increased expression of the full-length androgen receptor (AR-FL) and AR splice variants (AR-Vs) drives the progression of castration-resistant prostate cancer (CRPC). The levels of AR-FL and AR-V transcripts are often tightly correlated in individual CRPC samples, yet our understanding of how their expression is co-regulated is limited. Here, we report a role of c-Myc in accounting for coordinated AR-FL and AR-V expression. Analysis of gene-expression data from 159 metastatic CRPC samples and 2142 primary prostate tumors showed that the level of c-Myc is positively correlated with that of individual AR isoforms. A striking positive correlation also exists between the activity of the c-Myc pathway and the level of individual AR isoforms, between the level of c-Myc and the activity of the AR pathway, and between the activities of the two pathways. Moreover, the c-Myc signature is highly enriched in tumors expressing high levels of AR, as is the AR signature in c-Myc-high-expressing tumors. Using shRNA knockdown, we confirmed c-Myc regulation of expression and activity of AR-FL and AR-Vs in cell models and a patient-derived xenograft model. Mechanistically, c-Myc promotes the transcription of the AR gene and enhances the stabilit...Continue Reading

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Apr 21, 2020·EMBO Molecular Medicine·Tingting ZhangXia Sheng
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Methods Mentioned

BETA
xenograft
RNA-seq
co-immunoprecipitation
co-immunoprecipitation assay
reverse transcription-PCR
transfection
immunoprecipitation

Software Mentioned

RSEM
GSEA
R
STAR

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