American Association for Cancer Research
15417786mcr120618-sup-mcr-12-0618fig1-4.pdf (529.41 kB)

Supplementary Figures 1 - 4 from ERK and AKT Signaling Drive MED1 Overexpression in Prostate Cancer in Association with Elevated Proliferation and Tumorigenicity

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journal contribution
posted on 2023-04-03, 16:07 authored by Feng Jin, Shazia Irshad, Wei Yu, Madesh Belakavadi, Marina Chekmareva, Michael M. Ittmann, Cory Abate-Shen, Joseph D. Fondell

PDF file - 529K, Fig. S1. MED1 antibody specificity. Fig. S2. Anti-phospho-MED1 antibody specificity. Fig. S3. Inhibition of ERK or AKT signaling decreases MED1 phosphorylation and expression in prostate cancer cells. Fig. S4. Phospho-MED1 binds to the androgen receptor in prostate cancer cells.



MED1 is a key coactivator of the androgen receptor (AR) and other signal-activated transcription factors. Whereas MED1 is overexpressed in prostate cancer cell lines and is thought to coactivate distinct target genes involved in cell-cycle progression and castration-resistant growth, the underlying mechanisms by which MED1 becomes overexpressed and its oncogenic role in clinical prostate cancer have remained unclear. Here, we report that MED1 is overexpressed in the epithelium of clinically localized human prostate cancer patients, which correlated with elevated cellular proliferation. In a Nkx3.1:Pten mutant mouse model of prostate cancer that recapitulates the human disease, MED1 protein levels were markedly elevated in the epithelium of both invasive and castration-resistant adenocarcinoma prostate tissues. Mechanistic evidence showed that hyperactivated ERK and/or AKT signaling pathways promoted MED1 overexpression in prostate cancer cells. Notably, ectopic MED1 overexpression in prostate cancer xenografts significantly promoted tumor growth in nude mice. Furthermore, MED1 expression in prostate cancer cells promoted the expression of a number of novel genes involved in inflammation, cell proliferation, and survival. Together, these findings suggest that elevated MED1 is a critical molecular event associated with prostate oncogenesis.Visual Overview: Cancer Res; 11(7); 736–47. ©2013 AACR.