Overexpression of C-MYC oncogene in prostate cancer predicts biochemical recurrence

Abstract

Alterations of chromosome 8, including amplification at 8q24 harboring the C-MYC oncogene, have been noted as one of the most common chromosomal abnormalities in prostate cancer (CaP) progression. However, the frequency of C-MYC alterations in CaP has remained uncertain. A recent study, using a new anti-MYC antibody, described prevalent upregulation of nuclear C-MYC protein expression as an early oncogenic alteration in CaP. Further, we have recently reported regulation of C-MYC expression by ERG and a significant correlation between C-MYC overexpression and TMPRSS2-ERG fusion in early stage CaP. These emerging data suggest that increased C-MYC expression may be a critical and early oncogenic event driving CaP progression. In this study, we assessed whether C-MYC mRNA overexpression in primary prostate tumors was predictive of more aggressive tumor or disease progression. Our approach was to quantitatively determine C-MYC mRNA expression levels in laser capture micro-dissected tumor cells and matched benign epithelial cells in a radical prostatectomy cohort with long follow-up data available. On the basis of our results, we conclude that elevated C-MYC expression in primary prostate tumor is biologically relevant and may be a predictor of future biochemical recurrence.

Differential impact of RB status on E2F1 reprogramming in human cancer

“…Discovery of transcriptional networks that are uniquely associated with expanded E2F1 occupancy underscored activities of E2F1 beyond those linked to cell cycle control ( Figure 6, C and E), and identified heretofore underappreciated functions of E2F1. Notably, E2F1 reprogramming appears to be associated with increased Myc target gene expression, which is known to promote disease progression and poor outcome in this tumor type (79,80). These findings may also provide a molecular basis for recent observations in intestinal cancers, wherein RB pathway loss induces E2F3 and Myc cooperation (65).…”

Targeting CDK9: a promising therapeutic opportunity in prostate cancer

“…4). The role of CDK9 in regulation of these TFs has been reviewed (Kryštof et al 2012, Schmitz & Kracht 2016: Myc and NF-κB are overexpressed in CRPC and their simultaneous overexpression is a signature in the progression of PCa (Hawksworth et al 2010, Jin et al 2014. Moreover, in relapsed PCa that occurs via bypass pathway the underlying molecular defects are characterized by the upregulation of anti-apoptotic proteins like BCL-2, MCL-1 and XIAP (Krajewska et al 1996, Chaudhary et al 1999, Devi 2004.…”

Androgen-regulated metabolism and biosynthesis in prostate cancer

“…Cell cycle progression and metabolism are convergently regulated by multiple oncogenic signalling events and transcription factors, including c-Myc, which is overexpressed and predictive of poor prognosis in a subset of cases (Hawksworth et al 2010). Other examples include hypoxia-inducible factor 1a (HIF1A), which is associated with PCa metastasis (Ranasinghe et al 2013).…”