Receptor Expressed in Lymphoid Tissue (RELT) induces death in cancer cells, is upregulated in macrophages in response to tumor-conditioned medium and can translocate to the nucleus 3697

Abstract Description Receptor Expressed in Lymphoid Tissues (RELT) is a Tumor Necrosis Factor Receptor family member with two paralogs, RELL1 and RELL2 (collectively known as RELTfms). Expression of RELTfms in multiple cancerous cell lines was explored using western blotting, flow cytometry, and qRT-PCR. RELT and RELL1 protein expression were elevated in epithelial-derived lines, and the surface expression of RELT was highest in monocytes, whereas RELL2 protein expression was relatively consistent across different cell lines. Higher levels of RELT and RELL2 RNA transcripts were observed in leukocyte lines whereas RELL1 transcripts were higher in epithelial cell lines. Interestingly, RELT protein expression in Thp1-derived macrophages increased after exposure to tumor-conditioned medium (TCM). RELT overexpression increased cell death in the breast cancer cell line MDA-MB-231 (231), as assessed by flow cytometry for both AV/PI staining and Caspase 3/7 activation. Site-directed mutagenesis of the RELT gene was used to disrupt the binding of RELT to the OXSR1 kinase, and this mutation did not abrogate RELT-induced death, indicating that activation of the p38 pathway via OXSR1 phosphorylation of RELT is not required for apoptosis. Surprisingly, western blotting of cell fractions and immunofluorescence both demonstrated the ability of RELT to translocate to the nucleus. Further experiments are needed to determine the significance of RELT’s nuclear localization and upregulation in response to TCM. Topic Categories Cytokines and Chemokines and Their Receptors (CCR)