Disease relevance of BRS3

• BRS-3 receptors were often detected in prostate and pancreatic carcinomas and in pituitary adenomas [1].
• This enhanced selectivity should allow this analog to be useful for investigating the possible role of hBRS-3 in physiological or pathological processes [2].
• Of the 22 prostate cancer specimens analyzed by RT-PCR, 20 (91%) expressed GRPR mRNA, 3 (14%) showed NMBR mRNA, and 2 ( approximately 9%) revealed BRS-3 mRNA [3].
• Activation of bombesin receptor subtype-3 stimulates adhesion of lung cancer cells [4].
• We suggest that BRS-3 may be involved in invasion and metastasis of certain cancer cells, like small cell lung cancer cells, upon attachment to laminin [4].

High impact information on BRS3

• Stimulation of p125(FAK) tyrosine phosphorylation by hBRS-3 activation was not inhibited by the protein kinase C inhibitor, GF109203X, or thapsigargin, alone or in combination [5].
• We made two cell lines stably expressing the human BRS-3 (hBRS-3). hBRS-3 was overexpressed in the human non-small cell lung cancer cells, NCI-H1299, and the other was made in Balb 3T3 cells, which lack endogenous BRS-3 [6].
• The availability of these cell lines and the hBRS-3 ligand should facilitate identification of the natural ligand for BRS-3, its pharmacology, and cell biology [6].
• Expression of BRS-3 cDNA in Xenopus oocytes encodes a functional receptor that is specifically activated by BN-like peptides [7].
• BRS-3: a novel bombesin receptor subtype selectively expressed in testis and lung carcinoma cells [7].

Biological context of BRS3

• Chromosome mapping studies indicate that the BRS-3 gene is located on human chromosome X. BRS-3 mRNA expression in rat tissues is limited to secondary spermatocytes in testis [7].
• Development of bombesin analogs with conformationally restricted amino acid substitutions with enhanced selectivity for the orphan receptor human bombesin receptor subtype 3 [2].
• We have performed structure activity relationship studies on the high affinity peptide agonists [D-Phe6,beta-Ala11,Phe13,Nle14]Bn(6-14) and [D-Phe6,Phe13]Bn(6-13)propylamide, using their ability to mobilize intracellular calcium in BRS-3 transfected CHOGa-16 cells combined with receptor binding studies [8].
• The natural ligand for BRS-3 is currently unknown and little is known about the mechanisms regulating BRS-3 gene expression [9].
• 5. VV-H-7-induced hBRS-3 activation led to phosphorylation of p42/p44-MAP kinase in NCI-N417 cells, but did not stimulate cell proliferation [10].

Anatomical context of BRS3

• Immunoreactive GRP-R and BRS-3 receptors were in many cases predominantly confined to the plasma membrane and uniformly present on nearly all tumor cells [1].
• (177)Lu-AMBA also identified all NMB-expressing tumours, but did not detect BRS-3-expressing tumours or BRS-3-expressing pancreatic islets [11].
• In contrast, BRS-3 mRNA is widely expressed in a panel of human cell lines from all histological types of lung carcinoma [7].
• The adhesion of the cells to laminin induced by BRS-3 activation was accompanied by an increase in vinculin-like immunoreactivity and diminished in the presence of an anti-beta(1) integrin antibody, suggesting that the receptor activation stimulates focal adhesion formation [4].
• GRP-R mRNA predominated in the pregnant endometrium, whereas BRS-3 mRNA predominated in the membranes and placenta [12].

Associations of BRS3 with chemical compounds

• In the present study, we have attempted to develop a more selective hBRS-3 ligand by using two strategies: substitutions on phenyl ring of Apa11 and the substitution of other conformationally restricted amino acids into position 11 of [D-Tyr6,beta-Ala11,Phe13,Nle14]Bn(6-14) [2].
• 4. Endogenous hBRS-3 in NCI-N417 activated by VV-H-7 couples to phospholipase C resulting in changes of intracellular calcium, which is initially released from an inositol trisphosphate (IP(3))-sensitive store followed by a capacitive calcium entry from extracellular space [10].
• 1. The human orphan G-protein coupled receptor bombesin receptor subtype 3 (hBRS-3) was screened for peptide ligands by a Ca(2+)mobilization assay resulting in the purification and identification of two specific ligands, the naturally occurring VV-hemorphin-7 (VV-H-7) and LVV-hemorphin-7 (LVV-H-7), from human placental tissue [10].
• Eleven of 20 SCLC expressed NMB receptors, and 5/20 expressed BRS-3, compared with 4/13 and 1/13, respectively, in NSCLC cell lines [13].

Other interactions of BRS3

• Immunohistochemical detection of bombesin receptor subtypes GRP-R and BRS-3 in human tumors using novel antipeptide antibodies [1].
• An amplified fragment was detected for GRPR in seven of nine cases, for NMBR in six of 10 cases, and the BRS-3 in three of nine cases [14].
• In this study, we have isolated and characterized human genomic and complementary DNA (cDNA) clones encoding a new BN-like peptide receptor subtype, BN receptor subtype 3 (BRS-3) [7].
• A bombesin receptor subtype-3 peptide increases nuclear oncogene expression in a MEK-1 dependent manner in human lung cancer cells [15].
• The study demostrated that activation of BRS-3 may play an important role in wound repair of AHR [16].

Analytical, diagnostic and therapeutic context of BRS3

• In contrast, we could not detect BRS-3 mRNA in most tissue samples by rt-PCR [17].
• In these tissues, PCR for BRS-3 mRNA gave rise to an additional product (approximately 50 bp larger) [12].
• The results showed that: (1) There was few expression of BRS-3 mRNA in the control group [16].
• Amplification of mRNA from a human antral cell culture preparation demonstrated the presence of two receptors of the bombesin and gastrin-releasing peptide family, GRPR-1 and BRS-3 [18].

References