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dc.contributor.advisorHupp, Ted
dc.contributor.authorFourtouna, Argyro
dc.date.accessioned2010-11-16T11:54:58Z
dc.date.available2010-11-16T11:54:58Z
dc.date.issued2009
dc.identifier.urihttp://hdl.handle.net/1842/4302
dc.description.abstractProteomic technologies verified Anterior Gradient 2, AGR-2, as a protein over-expressed in human cancers, including breast, prostate and oesophagus cancers, with the ability to inhibit the tumour suppressor protein p53. AGR-2 gene is a hormone responsive gene with an unexpected induction by the anti-cancer drug tamoxifen highlighting the proto-oncogenic role of this protein. Anterior Gradient-2 encodes one protein that gives rise to two forms· the full length and the mature one. Full length bears a leader sequence that leads the protein to secretion. Localization studies of both forms of AGR-2 were performed using fluorescence microscopy and subcellular fractionation, in order to determine in which compartment the protein functions. Localization mutants of the mature and full length protein determined the exact sequence required for certain localization patterns. Once localization was confirmed, the mechanism of how Anterior Gradient-2 localization within the cell can inhibit p53 was initiated. Furthermore, novel peptide aptamers that bound to the protein were cloned into GFP vectors and their effect on AGR-2 was investigated. AGR-3, another member of the family, was also examined in terms of localization and function in MCF-7 cells. Yeast two hybrid analysis has identified potential nuclear and cytoplasmic binding partners for AGR-2, essential for the upstream or downstream regulation of the AGR-2 pathway. In conclusion, we present data showing models of how the Anterior Gradient protein family might function as drug-resistance survival factor in cancer as well as a p53 inhibitor, suggesting a multi-potent role of its members when it comes to trafficking, cellular localization and activation or inhibition pathways in cancer.en
dc.contributor.sponsorBreast Cancer Campaignen
dc.language.isoenen
dc.publisherThe University of Edinburghen
dc.subjectcanceren
dc.subjectAGR-2en
dc.subjectAGR-3en
dc.subjectP53en
dc.titleFunction of the anterior gradient protein family in canceren
dc.typeThesis or Dissertationen
dc.type.qualificationlevelDoctoralen
dc.type.qualificationnamePhD Doctor of Philosophyen


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