Background: Therapies that inhibit androgen receptor (AR) are needed for treatment of castration-resistant prostate cancer (CRPC). The ErbB3 binding protein 1 (EBP1) reduces protein expression of both AR and its target genes in CRPC. Although EBP1 regulates AR in hormone-sensitive prostate cancer cells, by both destabilizing AR mRNA and inhibiting protein translation, the mechanism of EBP1 down regulation of AR in CRPC is unknown.
Materials And Methods: Western blot and quantitative PCR analysis of cell lysates and polysomes were used to assess AR mRNA, protein expression and translation.
Results: In contrast to hormone- dependent cells, EBP1 did not change steady state levels of AR mRNA or AR mRNA stability in hormone refractory cells. EBP1 did slow protein translation of AR mRNA. The ErbB3/4 ligand heregulin further diminished AR translation in EBP1 -transfected cells, but not in control cells.
Conclusion: These studies suggest that one pathway of EBP1 down-regulation of AR levels may be lost in CRPC.
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