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Wnt signalling in prostate cancer stem-like cells

Davda, R; (2018) Wnt signalling in prostate cancer stem-like cells. Doctoral thesis (M.D(Res)), UCL (University College London). Green open access

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Abstract

The work reported in this thesis describes the characterisation of cell derived colonies from cancer cell lines and mechanisms of a key signalling pathway within these. PC3 cells were cultured at clonal density and resultant colony formation objectively described. Wnt signalling was investigated in colony types using a live [Ca2+]i assay. Exploratory work regarding ion channel gene and protein expression in 3 prostate cancer cell lines was performed. Preliminary investigation on the effects of MPRC (membrane potential regulating compounds) was performed using a cell proliferation assay. PC3 prostate cancer cells form distinct colonies with different morphologies. These different colony types can be characterised using quantitative parameters such as cell density and percentage cellularity, unlike previously employed visual only characteristics. PC3 cells form two types of colonies from a single cell. In this thesis these are termed holo/meroclones and paraclones. Cells within both colony types respond to Wnt activation, demonstrated by a response in free intracellular calcium [Ca2+]i . In addition, there is a suggestion of increased expression of, and translocation into the nucleus of the transcription factor co- activator β-catenin again in response to both Wnt 5A and Wnt 9B in both colony types. The characteristics of Wnt induced calcium release vary between different types of colonies. This is the first report of Wnt mediated [Ca2+]i release in response to both Wnt 5A and Wnt 9B in different PC3 colony types and the first report suggestive of β-catenin translocation following Wnt activation in colonies derived from stem-like cells.

Type: Thesis (Doctoral)
Qualification: M.D(Res)
Title: Wnt signalling in prostate cancer stem-like cells
Event: UCL (University College London)
Open access status: An open access version is available from UCL Discovery
Language: English
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
URI: https://discovery.ucl.ac.uk/id/eprint/10044056
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