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Studies on expressi...
Studies on expression and regulation of phospholipase A2 and cyclooxygenase 2 in gastrointestinal tissues with special reference to colorectal cancer
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- Dimberg, Jan (författare)
- Jönköping University,Linköpings universitet,Institutionen för biomedicin och kirurgi,Hälsouniversitetet,HHJ, Avdelningen för naturvetenskap och biomedicin,HHJ. Biomedicinsk plattform
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(creator_code:org_t)
- ISBN 9172195649
- Linköping : Linköping University Electronic Press, 1999
- Engelska 49 s.
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Serie: Linköping University Medical Dissertations, 0345-0082 ; 610
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Abstract
Ämnesord
Stäng
- The phospholipases A2 (PLA2s) are phospholipid hydrolyzing enzymes that in mammalian cells exist in several different isoform including cytosolic PLA2 (cPLA2), group I PLA2 (PLA2-I) and group II PLA2 (PLA2-ll). PLA2 is involved in production of inflammatory mediators, membrane remodelling, digestive functions and stimulation of prolifemtion. In addition. PLA2 supplies cyclooxygenase COX-1 and COX-2 with arachidonic acid for production of eicosanoids.Increased COX-2 expression and high concentrations of prostaglandins have been found in human colorectal adenocarcinomas and in rat colonic twnours. Studies implicate that there is a link between the tumourigenic effect of the tumour suppressor gene adenomatous polyposis coli (APC) and COX-2 up-regulation in mouse intestinal neoplasms. Mutations of the human APC gene are frequent in both sporadic and familial colorectal cancer and result in activation of p-catenin!T cell factor-4 (Tcf-4) mediated transcription of target genes which may contribute to colorectal tumourigenesis.The ontogenic development of rat gastrointestinal PLA2-I and PLA2-II and the influence of the exogenous glucocorticoid cortisone acetate were studied. The ontogeny of rat glandular stomach PLA2-I and PLA2-II gene expression is similar and seems to follow the general postnatal development of the gastrointestinal tract PLA2-II gene expression is different in the glandular stomach compared to ileum and forestomach during the neonatal period. Administration of the cortisone acetate, during the neonatal period, induced PLA2-I and PLA2-II gene expression in glandular stomach and ileum, respectively, au effect that may be related to maturation of the gastrointestinal tract.Gene expression of PLA2-II, cPLA2 and COX-2, protein levels of COX-2 and mutational analysis of APC were investigated in human colorectal tumours. COX-2 was dramatically up-regulated in tumours located in rectum and associated with the presence of APC mutations. Tcf-4 consensus sequences found in the COX-2 promoter were activated but APC/P-catenin/fcf-4 pathway may partly be involved in transcriptional regulation of the COX-2 gene. Neither induction of PLA2-II nor correlation in gene expression between cPLA2 and COX-2 were observed. 'These observations imply that other enzymes than PLA2 contribute to generate arachidonic acid for COX-2 mediated eicosanoid metabolism aud that PLA2-II seems to play a minor or no role in hllltlan colorectal cancer.
Nyckelord
- MEDICINE
- MEDICIN
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