Health Sciences Clinical Instructor
Division of Hematology/Oncology

Project title: Dissecting the function of Myc paralogs in human prostate cancer

Owen Witte, M.D. – UCLA
James Wohlschlegel, Ph.D. – UCLA
Justin Drake, Ph.D. – Rutgers
Josh Stuart, Ph.D. – UC Santa Cruz

Multidisciplinary expertise:
Cancer biology, proteomics, genomics/transcriptomics, functional genetic screening

Project Description:    
Myc proteins are multi-functional transcription factors whose deregulation is central to the initiation and maintenance of most human cancers. They are broadly thought to have redundant functions in development and tumorigenesis. In prostate cancer, the amplification and overexpression of c-Myc are common in prostate adenocarcinomas while N-Myc is amplified and overexpressed in 40% of neuroendocrine prostate cancers (NEPC). Prior work using a tissue recombination assay has shown that ectopic expression of c-Myc and activated AKT1 in human prostate epithelial cells produces poorly differentiated adenocarcinoma and squamous cell carcinoma while N-Myc and activated AKT1 generates mixed NEPC and prostate adenocarcinoma. These findings indicate that Myc paralogs may drive the pathogenesis of discrete cancer phenotypes through distinct biologic functions mediated by their regulatory complexes. The objective of this work is to characterize the core and divergent functions of c-Myc and N-Myc in prostate cancer through interactome, transcriptome, proteome, phosphoproteome, and functional analyses.