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dc.contributor.advisorGold, Elspeth
dc.contributor.advisorNicholson, Helen
dc.contributor.advisorReader, Karen
dc.contributor.authorCroxford, Kit Peter
dc.date.available2016-08-24T20:52:56Z
dc.date.copyright2016
dc.identifier.citationCroxford, K. P. (2016). TGF-β Superfamily Expression and Related Signalling in Low and High Grade Human Prostate Cancer (Thesis, Master of Science). University of Otago. Retrieved from http://hdl.handle.net/10523/6749en
dc.identifier.urihttp://hdl.handle.net/10523/6749
dc.description.abstractProstate cancer (PCa) is a common malignancy being the second most diagnosed cancer and sixth leading cause of male cancer death worldwide. PCa may present itself in several ways; slow growing and relatively benign, or fast growing and metastatic. There is currently no easy way of determining which form is present. There are two major issues with the detection of PCa; the lack of a non-invasive diagnostic biomarker, and difficulty in determining the prognosis. The transforming growth factor beta (TGF-β) superfamily is comprised of 30 proteins with strong regulatory effects on growth, differentiation and apoptosis, including TGF-β, activin and inhibin, and the bone morphogenic protein (BMP) and are associated with signalling through the SMA genes and mothers against decapentaplegic (SMAD) signalling proteins. This project aims to examine expression of the TGF-β superfamily and associated signalling pathways in human prostate cancer tissue to determine the potential role of TGF-β superfamily signalling in prostate cancer development. Gene expression was investigated using TGF-β focussed arrays, followed by validation with Western blotting in tissue samples from patients with low and high grade tumours to determine which signalling pathways were being utilized. The gene arrays showed significant alterations of several key genes between the low and high grade tumours. A two-fold increase of activin A and BMP3 and down regulation of BMP7 was observed. SMAD3 activity appeared to have decreased indicating increased non-canonical activin A signalling, as well as an up-regulation of metastasis related genes Plasminogen urokinase A, GSC and a down regulation of the growth inhibitory gene HIPK2. Western blot validation showed a statistically significant decrease in SMAD3 activation and SMAD4 content in high grade tumour tissue compared to low grade tumour tissue. This possible reduction in SMAD3 activation and SMAD4 content is consistent with the literature, showing that the progression of prostate cancer is associated with these changes. This study therefore suggests that decreased canonical signalling may play a role in prostate cancer development, although this study is unable to find a reason for this reduction and the direct cause it may have in prostate cancer progression. This finding highlights the potential for future study on SMAD3 and SMAD4 in relation to prostate cancer development.
dc.format.mimetypeapplication/pdf
dc.language.isoen
dc.publisherUniversity of Otago
dc.rightsAll 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.subjecttransforming growth factor beta
dc.subjectprostate cancer
dc.subjectbone morphogenetic protein
dc.subjectactivin
dc.subjectinhibin
dc.subjectnodal
dc.subjecttransforming growth factor beta superfamily
dc.titleTGF-β Superfamily Expression and Related Signalling in Low and High Grade Human Prostate Cancer
dc.typeThesis
dc.date.updated2016-08-24T20:27:20Z
dc.language.rfc3066en
thesis.degree.disciplineAnatomy
thesis.degree.nameMaster of Science
thesis.degree.grantorUniversity of Otago
thesis.degree.levelMasters
otago.openaccessOpen
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