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Cysteinyl leukotrie...
Cysteinyl leukotriene 1 receptor influences intestinal polyp incidence in a gender-specific manner in the ApcMin/+ mouse model
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- Savari, Sayeh (author)
- Karolinska Institutet,Lund University,Lunds universitet,Cellpatologi, Malmö,Forskargrupper vid Lunds universitet,Cell Pathology, Malmö,Lund University Research Groups,Skåne University Hospital
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Chandrashekar, Naveen Kumar (author)
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- Osman, Janina (author)
- Lund University,Lunds universitet,Cellpatologi, Malmö,Forskargrupper vid Lunds universitet,Cell Pathology, Malmö,Lund University Research Groups,Skåne University Hospital
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- Douglas, Desiree (author)
- Lund University,Lunds universitet,Cellpatologi, Malmö,Forskargrupper vid Lunds universitet,Cell Pathology, Malmö,Lund University Research Groups,Skåne University Hospital
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Bellamkond, Kishan (author)
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- Jönsson, Gunilla (author)
- Lund University,Lunds universitet,Cellpatologi, Malmö,Forskargrupper vid Lunds universitet,Cell Pathology, Malmö,Lund University Research Groups,Skåne University Hospital
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- Juhas, Maria (author)
- Lund University,Lunds universitet,Cellpatologi, Malmö,Forskargrupper vid Lunds universitet,Cell Pathology, Malmö,Lund University Research Groups,Skåne University Hospital
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- Greicius, Gediminas (author)
- Karolinska Institute,National Cancer Centre Singapore
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- Pettersson, Sven (author)
- Karolinska Institute,National Cancer Centre Singapore
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- Sjölander, Anita (author)
- Lund University,Lunds universitet,Cellpatologi, Malmö,Forskargrupper vid Lunds universitet,Cell Pathology, Malmö,Lund University Research Groups,Skåne University Hospital
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(creator_code:org_t)
- 2016-03-15
- 2016
- English.
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In: Carcinogenesis. - : Oxford University Press (OUP). - 0143-3334 .- 1460-2180. ; 37:5, s. 491-499
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Abstract
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- There is emerging literature emphasizing the role of inflammatory eicosanoids, including prostaglandins and leukotrienes, in cancer development. Increased expression of both the cysteinyl leukotriene receptor 1 (CysLTR1) and the enzyme responsible for the production of leukotrienes, 5-lipoxygenase (5-LOX), is associated with poor prognosis in patients with colorectal adenocarcinomas. Apc mutation is an early event in the development of sporadic and hereditary (FAP) colorectal cancer. We utilized the Apc(Min/+) mouse model of FAP/sporadic colorectal cancer to investigate the role of CysLTR1 in intestinal tumorigenesis by crossing Apc(Min/+) mice with mice lacking the Cysltr1 gene. We could observe a reduced tumor burden in the small intestine of double-mutant female (Cysltr1(-/-) Apc(Min/+)) but not double-mutant male mice, compared to gender-matched single-mutant (Cysltr1(+/+) Apc(Min/+)) mice. This reduction was in a Cysltr1 dependent manner, female double mutant mice having significantly reduced tumor formation compared to control littermates. The female double-mutant phenotype was accompanied with decreased systemic inflammation, as evidenced by significantly reduced serum levels of PGE2 and CysLTs, as well as increased CD3(+)CD8(+) T cell tumor infiltration. Furthermore, the reduced formation of polyps in double-mutant (Cysltr1(-/-) Apc(Min/+)) female mice could in part be explained by the cytotoxic action of CD3(+)CD8(+) T cells in the polyp and reduced nuclear accumulation of β-catenin in the epithelium of small intestinal polyps. Our results stress the important role that CysLTR1 plays in colorectal cancer and its potential as a therapeutic target in cancer therapy.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Savari, Sayeh
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Chandrashekar, N ...
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Osman, Janina
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Douglas, Desiree
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Bellamkond, Kish ...
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Jönsson, Gunilla
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show more...
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Juhas, Maria
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Greicius, Gedimi ...
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Pettersson, Sven
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Sjölander, Anita
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Cell and Molecul ...
- Articles in the publication
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Carcinogenesis
- By the university
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Lund University
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Karolinska Institutet