Glucose and cAMP regulation of Wnt/beta-catenin signaling pathway

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dc.contributor.advisor Shepherd, P en
dc.contributor.advisor Cognard, E en
dc.contributor.author Chen, Leilei en
dc.date.accessioned 2012-03-08T00:16:07Z en
dc.date.issued 2012 en
dc.identifier.uri http://hdl.handle.net/2292/13381 en
dc.description Full text is available to authenticated members of The University of Auckland only. en
dc.description.abstract The canonical Wnt/β-catenin signaling pathway is recently identified to regulate cellular metabolism processes and act as a “glucose sensor” in certain cell lines. Results of our laboratory have shown that glucose can increase cAMP levels to regulate the levels of β-catenin protein in INS-1E β-cells. Activation of the canonical Wnt signaling pathway can decrease the rate of β-catenin targeting for ubiquitin-mediated degradation, so the hallmark of the signaling pathway activation is the accumulation of β-catenin protein levels in the cells. Cytoplamic β-catenin proteins can translocate into the nucleus, and binds with LEF/TCF transcription factor to induce Wnt-target gene expression. Dysregulation of Wnt/β-catenin signaling pathway is related to the development of type 2 diabetes mellitus and cancer. Thus, it is important to study the regulation of this pathway in different cell lines. This study investigated the effect of glucose and cAMP on β-catenin protein levels in different cell lines. We demonstrated that glucose did not acutely regulate β-catenin protein levels in GLUTag cells, αTC1-9 cells and three cancer cell lines. However, glucose could have a long-term effect on active and total β-catenin levels in GLUTag cells. We found that forskolin-induced cAMP/PKA signaling pathway could enhance phosphorylation of β-catenin at Serine 552 and Serine 675 in GLUTag cells and three cancer cell lines. Our findings indicated that cAMP signaling pathway can regulate phosphorylated β-catenin levels in different cancer cell lines and the findings have potentially very important implications for the inhibition of Wnt/β-catenin signaling pathway in cancer cell lines. en
dc.publisher ResearchSpace@Auckland en
dc.relation.ispartof Masters Thesis - University of Auckland en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. en
dc.rights Restricted Item. Available to authenticated members of The University of Auckland. en
dc.rights.uri https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm en
dc.rights.uri http://creativecommons.org/licenses/by-nc-sa/3.0/nz/ en
dc.title Glucose and cAMP regulation of Wnt/beta-catenin signaling pathway en
dc.type Thesis en
thesis.degree.grantor The University of Auckland en
thesis.degree.level Masters en
dc.rights.holder Copyright: The author en
pubs.elements-id 314828 en
pubs.record-created-at-source-date 2012-03-08 en


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