c-Myc antagonises the transcriptional activity of the androgen receptor in prostate cancer affecting key gene networks.

Barfeld, S; Urbanucci, A; Itkonen, H; Fazli, L; Hicks, J; Thiede, B; Rennie, P; Yegnasubramanian, S; DeMarzo, A; Mills, I

Journal article

c-Myc antagonises the transcriptional activity of the androgen receptor in prostate cancer affecting key gene networks.

Abstract:: Prostate cancer (PCa) is the most common non-cutaneous cancer in men. The androgen receptor (AR), a ligand-activated transcription factor, constitutes the main drug target for advanced cases of the disease. However, a variety of other transcription factors and signaling networks have been shown to be altered in patients and to influence AR activity. Amongst these, the oncogenic transcription factor c-Myc has been studied extensively in multiple malignancies and elevated protein levels of c-Myc are commonly observed in PCa. Its impact on AR activity, however, remains elusive. In this study, we assessed the impact of c-Myc overexpression on AR activity and transcriptional output in a PCa cell line model and validated the antagonistic effect of c-MYC on AR-targets in patient samples. We found that c-Myc overexpression partially reprogrammed AR chromatin occupancy and was associated with altered histone marks distribution, most notably H3K4me1 and H3K27me3. We found c-Myc and the AR co-occupy a substantial number of binding sites and these exhibited enhancer-like characteristics. Interestingly, c-Myc overexpression antagonised clinically relevant AR target genes. Therefore, as an example, we validated the antagonistic relationship between c-Myc and two AR target genes, KLK3 (alias PSA, prostate specific antigen), and Glycine N-Methyltransferase (GNMT), in patient samples. Our findings provide unbiased evidence that MYC overexpression deregulates the AR transcriptional program, which is thought to be a driving force in PCa.

Publication status:: Published

Peer review status:: Peer reviewed

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APA Style

Barfeld, S., Urbanucci, A., Itkonen, H., Fazli, L., Hicks, J., Thiede, B., Rennie, P., Yegnasubramanian, S., DeMarzo, A., & Mills, I. (2017). c-Myc antagonises the transcriptional activity of the androgen receptor in prostate cancer affecting key gene networks. EBioMedicine, 18, 83–93.

MLA Style

Barfeld, S, et al. “c-Myc Antagonises the Transcriptional Activity of the Androgen Receptor in Prostate Cancer Affecting Key Gene Networks.” EBioMedicine, vol. 18, 2017, pp. 83–93.

Chicago Style

Barfeld, S, A Urbanucci, H Itkonen, et al. 2017. “c-Myc Antagonises the Transcriptional Activity of the Androgen Receptor in Prostate Cancer Affecting Key Gene Networks.” EBioMedicine 18: 83–93.
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