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Differential protein expression on the cell surface of normal epithelial and prostate cancer cells.

Hastie, C.L.; (2007) Differential protein expression on the cell surface of normal epithelial and prostate cancer cells. Doctoral thesis , University of London. Green open access

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Abstract

Prostate cancer is the most frequently diagnosed cancer in men in Western countries. Clinically localized disease can be cured with surgery or radiotherapy, but once the disease has advanced or spread, there are no curative treatments. The aim of this thesis is to compare protein expression in a pair of normal epithelial and prostate cancer cells derived from the same patient and to determine the effect of interferon y on this expression pattern. Proteins that are differentially expressed or change in expression in response to y interferon might be of clinical value as biomarkers or therapeutic targets. Biotin labelling followed by avidin chromatography was used to obtain membrane protein enriched lysates from a pair of cell lines derived from normal epithelium (1542 NPX) and prostate cancer (1542 CP3TX) from the same patient. These proteins were resolved and identified using SDS PAGE, coomassie staining and mass spectrometry. The same protocol was used to identify proteins differentially expressed on stimulation with interferon y. The proteins identified were subject to further analysis, particularly annexin II (All), which was interferon-regulated. The expression of this protein was down regulated in the cancer cell line within four hours of interferon y stimulation. This expression pattern was found to be cell surface specific as the total cellular expression of All remained unchanged, as confirmed by immunofluorescence. All down regulation also reduced the invasive potential of the cancer cells. Re-introduction of All into LNCaP cells, which do not express the protein, led to an increase in their invasive capacity. The mechanism regulating this cell surface specific effect was explored. It was discovered that inhibition of the ATP binding cassette transporter ABCA1 prevented surface AH expression. Protection of ABCA1 from calpain mediated degradation, maintained AH expression even in the presence of interferon y. These findings led to the development of a model of interferon y action on All involving phosphorylation of ABCA1 as a signal for targeted degradation by calpain II.

Type: Thesis (Doctoral)
Title: Differential protein expression on the cell surface of normal epithelial and prostate cancer cells.
Identifier: PQ ETD:592870
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by Proquest
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci > Department of Targeted Intervention
URI: https://discovery.ucl.ac.uk/id/eprint/1445546
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