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Association Between...
Association Between Adenomatosis Polyposis Coli Functional Status and Microsomal Prostaglandin E Synthase-1 Expression in Colorectal Cancer
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- Elander, Nils (författare)
- Linköpings universitet,Cellbiologi,Hälsouniversitetet
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- Zhou, Jianlin (författare)
- Linköpings universitet,Institutionen för klinisk och experimentell medicin,Hälsouniversitetet
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- Ungerbäck, Jonas (författare)
- Linköpings universitet,Cellbiologi,Hälsouniversitetet
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- Dimberg, Jan (författare)
- Jönköping University
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- Söderkvist, Peter (författare)
- Linköpings universitet,Cellbiologi,Hälsouniversitetet
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(creator_code:org_t)
- 2008-11-26
- 2009
- Engelska.
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Ingår i: Molecular Carcinogenesis. - : Wiley. - 0899-1987 .- 1098-2744. ; 48:5, s. 401-407
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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.
Nyckelord
- cyclooxygenase 2
- Prostaglandin E-2
- beta-catenin
- adenomatosis polyposis coli (APC)
- microsomal prostaglandin E synthase-1 (mPGES-1)
- colorectal cancer
- MEDICINE
- MEDICIN
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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