The Effects of Activin B and Activin C on the Growth and Migration of Prostate Cancer Cells

Abstract

Prostate cancer (PCa) is the most diagnosed cancer in New Zealand men and is one of the leading causes of male cancer related death globally. Current diagnostic and prognostic tools for PCa are unable to differentiate between aggressive or non-aggressive forms of PCa, or to predict whether tumours will metastasize. Additionally, a lack of non-invasive treatment options for lower grade PCa leads to overtreatment of the disease and subsequent unnecessary harm and long-term negative side effects from invasive treatments. Little is known about the regulation of the healthy prostate, or factors leading to the development and progression of prostate tumours. This thesis aimed to further the understanding of healthy prostate development, disease progression, as well as to present new prognostic and diagnostic markers to validate and improve prostate cancer outcomes. This research studied activin B and activin C and tested the hypotheses that these activins alter growth and migration in the healthy and cancerous prostate. Additionally, it sought to elucidate the signalling pathways that these activins act through, showing the first activin C prostate signalling data to date. To test these hypotheses; healthy and cancerous prostate cells were stably transfected to overexpress activin B and activin C. Growth, migration and signalling assays were performed using stably transfected cells to measure how activins affect the normal and cancerous prostate. These results have shown activin B promotes proliferation (fold change = 1.17, p < 0.0001) and migration (fold change = 1.65, p < 0.0001) of PC3 cells. Additionally, this research showed for the first time that activin C promotes PNT1A cell growth (fold change = 1.14, p < 0.001), inhibits PC3 cell growth (fold change = 0.90, p < 0.05), and increased PC3 cell migration (fold change = 1.64, p < 0.0001). This research highlighted new data to further the understanding of healthy and cancerous prostate growth and development, as well as showing new prognostic and diagnostic markers that may have important clinical value