Novel Biomarkers for Prostate Cancer Progression
Type of Proposal
Oral presentation
Faculty
Faculty of Science
Faculty Sponsor
Dr. Lisa Porter
Proposal
Prostate cancer is the most frequently diagnosed type of cancer in Canadian men, with 1 in every 8 men being diagnosed with it at some point in their life. It is, however, often very manageable if detected early enough. Determining which patients have a high potential for progression remains a significant barrier in the treatment of this disease. Using data collected from prostate cancer patients, the University of Windsor computer science department developed technology to isolate novel RNA splice variants that are differentially expressed through progression of prostate cancer. This could indicate a mechanism by which prostate cancer evolves and could provide valuable prognostic markers. To validate the biological significance of these RNA variants, RNA was collected from prostate cells at various stages of progression to aggressive, androgen-independent cancer. Expression of the various transcript variants was analyzed using quantitative-real-time-PCR. One particular splice variant that has emerged as potentially important is from the WWP2 gene, an E3 ubiquitin ligase which has previously been shown to down-regulate the tumour suppressor PTEN. We have demonstrated that protein expression patterns mimic that of the RNA transcript, being increased abruptly at stage III prostate cancer. We are currently investigating how this specific splice pattern can alter WWP2 expression by knocking down expression of the transcript and testing the effects on cell growth and proliferation through various cell culture assays. Expression profiles of these splice variants could act as important biomarkers indicating the severity and likelihood of progression. This could be an invaluable tool in preventing overtreatment leaving life-long side effects of treatment for cancers not likely to progress. Furthermore targeting some of the gene products, like WWP2, may represent a valuable treatment option for aggressive late stage cancers.
Start Date
31-3-2017 9:00 AM
End Date
31-3-2017 10:20 AM
Novel Biomarkers for Prostate Cancer Progression
Prostate cancer is the most frequently diagnosed type of cancer in Canadian men, with 1 in every 8 men being diagnosed with it at some point in their life. It is, however, often very manageable if detected early enough. Determining which patients have a high potential for progression remains a significant barrier in the treatment of this disease. Using data collected from prostate cancer patients, the University of Windsor computer science department developed technology to isolate novel RNA splice variants that are differentially expressed through progression of prostate cancer. This could indicate a mechanism by which prostate cancer evolves and could provide valuable prognostic markers. To validate the biological significance of these RNA variants, RNA was collected from prostate cells at various stages of progression to aggressive, androgen-independent cancer. Expression of the various transcript variants was analyzed using quantitative-real-time-PCR. One particular splice variant that has emerged as potentially important is from the WWP2 gene, an E3 ubiquitin ligase which has previously been shown to down-regulate the tumour suppressor PTEN. We have demonstrated that protein expression patterns mimic that of the RNA transcript, being increased abruptly at stage III prostate cancer. We are currently investigating how this specific splice pattern can alter WWP2 expression by knocking down expression of the transcript and testing the effects on cell growth and proliferation through various cell culture assays. Expression profiles of these splice variants could act as important biomarkers indicating the severity and likelihood of progression. This could be an invaluable tool in preventing overtreatment leaving life-long side effects of treatment for cancers not likely to progress. Furthermore targeting some of the gene products, like WWP2, may represent a valuable treatment option for aggressive late stage cancers.