Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8347396 | Peptides | 2018 | 14 Pages |
Abstract
Human bombesin receptors, GRPR and NMBR, are two of the most frequently overexpressed G-protein-coupled-receptors by lung-cancers. Recently, GRPR/NMBR are receiving considerable attention because they act as growth factor receptors often in an autocrine manner in different lung-cancers, affect tumor angiogenesis, their inhibition increases the cytotoxic potency of tyrosine-kinase inhibitors reducing lung-cancer cellular resistance/survival and their overexpression can be used for sensitive tumor localization as well as to target cytotoxic agents to the cancer. The orphan BRS-3-receptor, because of homology is classified as a bombesin receptor but has received little attention, despite the fact that it is also reported in a number of studies in lung-cancer cells and has growth effects in these cells. To address its potential importance, in this study, we examined the frequency/relative quantitative expression of human BRS-3 compared to GRPR/NMBR and the effects of its activation on cell-signaling/growth in 13 different human lung-cancer cell-lines. Our results showed that BRS-3 receptor is expressed in 92% of the cell-lines and that it is functional in these cells, because its activation stimulates phospholipase-C with breakdown of phosphoinositides and changes in cytosolic calcium, stimulates ERK/MAPK and stimulates cell growth by EGFR transactivation in some, but not all, the lung-cancer cell-lines. These results suggest that human BRS-3, similar to GRPR/NMBR, is frequently ectopically-expressed by lung-cancer cells in which, it is functional, affecting cell signaling/growth. These results suggest that similar to GRPR/NMBR, BRS-3 should receive increased attention as possible approach for the development of novel treatments and/or diagnosis in lung-cancer.
Keywords
BNRERKEC50GPCRPLCGRPGRPRNMBDulbecco’s Minimum Essential MediumEGFRbombesin receptorsneuromedin BNMBRneuromedin B receptorBombesin receptor subtype-3BRS-3bovine serum albumin fraction VPBSIC50qPCRDMEMFBSBSAG-protein-coupled receptorinositol phosphateMAPKMitogen activated protein kinasesHumanBombesinSCLCCNSquantitative real time PCRnonsmall cell lung cancerNSCLCSmall cell lung cancerfetal bovine serummouse embryonic fibroblast cellscentral nervous systemPhosphate buffered salinephospholipase CMouseRatpolymerase chain reactionPCRgastrin-releasing peptideextracellular signal-regulated kinasesEpidermal growth factor receptorgastrin-releasing peptide receptor
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Authors
Paola Moreno, Samuel A. Mantey, Suk H. Lee, Irene Ramos-Álvarez, Terry W. Moody, Robert T. Jensen,