dc.contributor.author | Brudvik, Kristoffer W | |
dc.contributor.author | Paulsen, Jan E | |
dc.contributor.author | Aandahl, Einar M | |
dc.contributor.author | Roald, Borghild | |
dc.contributor.author | Taskén, Kjetil | |
dc.date.accessioned | 2015-10-20T10:50:38Z | |
dc.date.available | 2015-10-20T10:50:38Z | |
dc.date.issued | 2011 | |
dc.identifier.citation | Molecular Cancer. 2011 Dec 15;10(1):149 | |
dc.identifier.uri | http://hdl.handle.net/10852/46904 | |
dc.description.abstract | Background
The adenomatous polyposis coli (APC) protein is part of the destruction complex controlling proteosomal degradation of β-catenin and limiting its nuclear translocation, which is thought to play a gate-keeping role in colorectal cancer. The destruction complex is inhibited by Wnt-Frz and prostaglandin E2 (PGE2) - PI-3 kinase pathways. Recent reports show that PGE2-induced phosphorylation of β-catenin by protein kinase A (PKA) increases nuclear translocation indicating two mechanisms of action of PGE2 on β-catenin homeostasis.
Findings
Treatment of Apc
Min/+ mice that spontaneously develop intestinal adenomas with a PKA antagonist (Rp-8-Br-cAMPS) selectively targeting only the latter pathway reduced tumor load, but not the number of adenomas. Immunohistochemical characterization of intestines from treated and control animals revealed that expression of β-catenin, β-catenin nuclear translocation and expression of the β-catenin target genes c-Myc and COX-2 were significantly down-regulated upon Rp-8-Br-cAMPS treatment. Parallel experiments in a human colon cancer cell line (HCT116) revealed that Rp-8-Br-cAMPS blocked PGE2-induced β-catenin phosphorylation and c-Myc upregulation.
Conclusion
Based on our findings we suggest that PGE2 act through PKA to promote β-catenin nuclear translocation and tumor development in Apc
Min/+ mice in vivo, indicating that the direct regulatory effect of PKA on β-catenin nuclear translocation is operative in intestinal cancer. | |
dc.language.iso | eng | |
dc.rights | Brudvik et al; licensee BioMed Central Ltd. | |
dc.rights | Attribution 2.0 Generic | |
dc.rights.uri | http://creativecommons.org/licenses/by/2.0/ | |
dc.title | Protein kinase A antagonist inhibits β-catenin nuclear translocation, c-Myc and COX-2 expression and tumor promotion in Apc
Min/+ mice | |
dc.type | Journal article | |
dc.date.updated | 2015-10-20T10:50:38Z | |
dc.creator.author | Brudvik, Kristoffer W | |
dc.creator.author | Paulsen, Jan E | |
dc.creator.author | Aandahl, Einar M | |
dc.creator.author | Roald, Borghild | |
dc.creator.author | Taskén, Kjetil | |
dc.identifier.doi | http://dx.doi.org/10.1186/1476-4598-10-149 | |
dc.identifier.urn | URN:NBN:no-51069 | |
dc.type.document | Tidsskriftartikkel | |
dc.type.peerreviewed | Peer reviewed | |
dc.identifier.fulltext | Fulltext https://www.duo.uio.no/bitstream/handle/10852/46904/1/12943_2011_Article_979.pdf | |
dc.type.version | PublishedVersion | |
cristin.articleid | 149 | |