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Open Access Green as soon as Postprint is submitted to ZB.
BLT2 is expressed in PanINs, IPMNs, pancreatic cancer and stimulates tumour cell proliferation.
Br. J. Cancer 99, 1064-1073 (2008)
Pancreatic cancer has an abysmal prognosis. Targets for early detection, prevention and therapy are desperately needed. Inflammatory pathways have an important impact on tumour growth and progression. Expression of BLT2 (the second leukotriene B(4) receptor) was investigated by real-time RT-PCR and immunohistochemistry. Cell proliferation was studied after stable transfection with BLT2, after treatment with siRNA and Compound A as an agonist. BLT2 is expressed in all pancreatic cancer cell lines. Results from real-time RT-PCR revealed significant overexpression of BLT2 in malignant intraductal papillary mucinous neoplasias (IPMNs) and pancreatic adenocarcinoma. Intense staining was evident in IPMNs, infiltrating tumour cells and advanced pancreatic intraepithelial neoplasias (PanINs) but not in normal ductal cells. Overexpression of BLT2 as well as stimulation of Colo357, Panc-1 and AsPC1 cells with Compound A caused a significant increase in tumour cell proliferation, an effect reversed after siRNA treatment. This study demonstrates for the first time the expression of BLT2 in the pancreas and overexpression in pancreatic cancers and malignant IPMNs in particular. Upregulation of BLT2 is already evident in precursor lesions (PanINs, IPMNs). Overexpression of this receptor leads to significant growth stimulation. Therefore, we suggest BLT2 as a new target for chemoprevention and therapy for pancreatic cancer.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
BLT2; PanIN; IPMN; pancreatic cancer; leukotriene B4
Language
english
Publication Year
2008
HGF-reported in Year
0
ISSN (print) / ISBN
0007-0920
e-ISSN
1532-1827
Journal
British Journal of Cancer BJC
Quellenangaben
Volume: 99,
Issue: 7,
Pages: 1064-1073
Publisher
Nature Publishing Group
Reviewing status
Peer reviewed
Institute(s)
Institute of Pathology (PATH)
POF-Topic(s)
30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Research field(s)
Enabling and Novel Technologies
PSP Element(s)
G-500300-001
Scopus ID
53049109168
Erfassungsdatum
2008-12-09