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- Elander, NilsLinköpings universitet,Cellbiologi,Hälsouniversitetet (author)
Association Between Adenomatosis Polyposis Coli Functional Status and Microsomal Prostaglandin E Synthase-1 Expression in Colorectal Cancer
- Article/chapterEnglish2009
Publisher, publication year, extent ...
- 2008-11-26
- Wiley,2009
- printrdacarrier
Numbers
- LIBRIS-ID:oai:DiVA.org:liu-18549
- https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-18549URI
- https://doi.org/10.1002/mc.20500DOI
Supplementary language notes
- Language:English
- Summary in:English
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- SwePubSwePub
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Notes
- Bioactive metabolites downstream of cyclooxygenase-2 (COX-2) generated prostaglandin H-2 (PGH(2)), in particular prostaglandin E-2 (PGE(2)), are thought to play critical roles during the development of colorectal tumors. Previous reports reveal that defects of the tumor suppressor adenomatosis polyposis coli (APC) contribute to COX-2 upregulation in colon tumor cells. We investigated whether a similar relation was present between APC functional status and the expression of microsomal prostaglandin E synthase-1 (mPGES-1), which acts downstream of COX-2 and catalyses the terminal conversion of PGH(2) into PGE(2). Surprisingly, mPGES-1 mRNA and protein levels were upregulated upon induction of a wild type-APC carrying vector in HT29 colon cancer cells, and downregulated following siRNA silencing of APC in HCT-116 cells. mPGES-1 was overall enhanced in human colorectal tumor specimens versus corresponding non-tumor mucosa and, in accordance with data on HT29 and HCT116 cells, higher levels of mPGES-1 were observed among tumors carrying wild type versus mutant APC. RNAi silencing of beta-catenin and luciferase assays regarding the mPGES-1 promoter region did not reveal a role for APC or beta-catenin/Tcf in controlling mPGES-1 gene transcription. However, RNA degradation assays in HT29 cells revealed a suppressed degradation of mPGES-1 in the presence of wild type APC, implying that mPGES-1 mRNA is stabilized in the APC wild type state. Collectively, we demonstrate a novel association between APC functional status and mPGFS-1 expression in colorectal tumor cells, being most likely related to reduced mPGES-1 mRNA degradation rate in the APC wild type state.
Subject headings and genre
- cyclooxygenase 2
- Prostaglandin E-2
- beta-catenin
- adenomatosis polyposis coli (APC)
- microsomal prostaglandin E synthase-1 (mPGES-1)
- colorectal cancer
- MEDICINE
- MEDICIN
Added entries (persons, corporate bodies, meetings, titles ...)
- Zhou, JianlinLinköpings universitet,Institutionen för klinisk och experimentell medicin,Hälsouniversitetet(Swepub:liu)jiazh28 (author)
- Ungerbäck, JonasLinköpings universitet,Cellbiologi,Hälsouniversitetet(Swepub:liu)jonun74 (author)
- Dimberg, JanJönköping University (author)
- Söderkvist, PeterLinköpings universitet,Cellbiologi,Hälsouniversitetet(Swepub:liu)petso43 (author)
- Linköpings universitetCellbiologi (creator_code:org_t)
Related titles
- In:Molecular Carcinogenesis: Wiley48:5, s. 401-4070899-19871098-2744
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