Regulation of Cysteinyl Leukotriene Receptor 2 Expression--A Potential Anti-Tumor Mechanism.

Background The cysteinyl leukotrienes receptors (CysLTRs) are implicated in many different pathological conditions, such as inflammation and cancer. We have previously shown that colon cancer patients with high CysLT1R and low CysLT2R expression demonstrate poor prognosis. Therefore, we wanted to investigate ways for the transcriptional regulation of CysLT2R, which still remains to be poorly understood. Methodology/Principal Findings We investigated the potential role of the anti-tumorigenic interferon &3x03B1; (IFN-&3x03B1;) and the mitogenic epidermal growth factor (EGF) on CysLT2R regulation using non-transformed intestinal epithelial cell lines and colon cancer cells to elucidate the effects on the CysLT2R expression and regulation. This was done using Western blot, qPCR, luciferase reporter assay and a colon cancer patient array. We found a binding site for the transcription factor IRF-7 in the putative promoter region of CysLT2R. This site was involved in the IFN-&3x03B1; induced activity of the CysLT2R luciferase reporter assay. In addition, IFN-&3x03B1; induced the activity of the differentiation marker alkaline phosphatase along with the expression of mucin-2, which protects the epithelial layer from damage. Interestingly, EGF suppressed both the expression and promoter activity of the CysLT2R. E-boxes present in the CysLT2R putative promoter region were involved in the suppressing effect. CysLT2R signaling was able to suppress cell migration that was induced by EGF signaling. Conclusions/Significance The patient array showed that aggressive tumors generally expressed less IFN-&3x03B1; receptor and more EGFR. Interestingly, there was a negative correlation between CysLT2R and EGFR expression. Our data strengthens the idea that there is a protective role against tumor progression for CysLT2R and that it highlights new possibilities to regulate the CysLT2R. [ABSTRACT FROM AUTHOR]