Investigating the roles of caveolae and PTRF in prostate cancer
|dc.contributor.author||Low, Jin Yih|
|dc.identifier.citation||Low, J. Y. (2016). Investigating the roles of caveolae and PTRF in prostate cancer (Thesis, Doctor of Philosophy). University of Otago. Retrieved from http://hdl.handle.net/10523/6350||en|
|dc.description.abstract||Prostate cancer poses a significant health threat to men world-wide. Caveolae are “cave-like” invaginations that are found in the plasma membrane. Polymerase I and transcript release factor (PTRF) is reported to be involved in the formation of caveolae. Expression of PTRF and caveolae are lost in prostate cancer cell lines and tissues, while restoration of PTRF expression leads to formation of caveolae and reduced aggressive phenotypes in vitro and in vivo. However, it is unclear whether the effect seen is due to PTRF itself or the restoration of caveolae. This study examines whether PTRF or caveolae are involved in prostate cancer. Bioinformatic tools were used to analyze the changes in expression of caveolae related molecules and the possible associated signalling pathway molecules. Then, a normal prostate cell line (RWPE-1) was characterised to identify the expression of caveolae and PTRF in these cells. Next, PTRF was knocked down and caveolae were disrupted separately in the characterised normal prostate cells to identify the effect of losing these two components. Changes in phenotypes and cellular signalling were investigated. The possible involvement of epigenetic mechanisms that may act up-stream of PTRF to control its expression were also investigated. Bioinformatic analysis provided an insight into the possible changes in expression of the examined caveolae related and signalling pathway molecules in normal and prostate cancer cell lines. Characterisation of the normal prostate cell line revealed the presence of PTRF and caveolae in these cell lines when compared to prostate cancer cell lines. When PTRF expression was knocked down and caveolae were disrupted in these normal prostate cells, reduced caveolae numbers were observed. Following both treatments increased proliferation, migration and invasion was observed in the normal prostate cells. However, cell signalling arrays showed a different pattern of signalling molecule activation. Increased p-STAT3 was observed after knocking down PTRF, while disrupting caveolae alone resulted in increased expression of p-ERK1/2. Epigenetic analysis revealed that PTRF may be regulated by histone deacetylation in the androgen dependent cell line, LNCaP cells, which is a model for early stage of prostate cancer. Collectively, both PTRF and caveolae may be involved in promoting cancer-like behaviours in normal prostate cells when they are down-regulated, however these two components may act through different signalling pathways. Also, histone deacetylation may affect the expression of PTRF in an in vitro model for early stages of prostate cancer. Understanding of the importance of PTRF and caveolae in prostate cancer development may provide clinicians to identify better therapeutic targets that may benefit prostate cancer patients in the future.|
|dc.publisher||University of Otago|
|dc.rights||All items in OUR Archive are provided for private study and research purposes and are protected by copyright with all rights reserved unless otherwise indicated.|
|dc.title||Investigating the roles of caveolae and PTRF in prostate cancer|
|thesis.degree.name||Doctor of Philosophy|
|thesis.degree.grantor||University of Otago|
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