Expression of the leukotriene D4 receptor CysLT1, COX-2, and other cell survival factors in colorectal adenocarcinomas.

Abstract:

BACKGROUND & AIMS:The effects of leukotriene (LT) D(4) on intestinal epithelial cells govern events that are involved in cell survival and colon cancer, notably increased expression of cyclooxygenase (COX)-2 and enhanced production of prostaglandin E(2). We investigated possible correlations between distribution of the recently described LTD(4) receptor CysLT(1)R and factors previously shown to be up-regulated by LTD(4) as well as clinicopathologic traits. METHODS:Immunohistochemistry and in situ hybridization were performed on tissue arrays, which were made using colorectal cancer samples from 84 patients. RESULTS:CysLT(1)R was significantly correlated to COX-2, 5-lipoxygenase, and Bcl-x(L). Male subjects more often exhibited high levels of this receptor relative to female subjects, and Dukes' B patients with elevated CysLT(1)R expression showed markedly poorer survival than those with low-level expression. Furthermore, this was paralleled by an increased viability of CysLT(1)R-overexpressing cells in a colon cancer cell line. CONCLUSIONS:Our results further implicate the involvement of LTs in colorectal carcinoma. Based on our present and earlier findings, we propose that LT/CysLT(1)R signaling facilitates survival of colon cancer cells, which may affect disease outcome. Like COX-2, LTs are accessible targets for pharmacologic treatment.

journal_name

Gastroenterology

journal_title

Gastroenterology

authors

Ohd JF,Nielsen CK,Campbell J,Landberg G,Löfberg H,Sjölander A

doi

10.1053/gast.2003.50011

keywords:

subject

Has Abstract

pub_date

2003-01-01 00:00:00

pages

57-70

issue

1

eissn

0016-5085

issn

1528-0012

pii

S0016508503500191

journal_volume

124

pub_type

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