GRP receptors are present in non small cell lung cancer cells.
Previously, GRP receptors were characterized in small cell lung cancer cells and here non-small cell lung cancer (NSCLC) cells were investigated: (125I-Tyr4) bombesin (BN) or 125I-GRP bound with high affinity to NCI-H720 (lung carcinoid) and NCI-H1299 (large cell carcinoma) cells. Binding was specific, time dependent, and saturable. Specific (125I-Tyr4)BN binding to NCI-H1299 cells was inhibited with high affinity by GRP, BN, GRP14-27, (D-Phe6)BN6-13methyl ester, moderate affinity by NMB, and low affinity by GRP1-16. BN (10 nM) transiently elevated cytosolic calcium in a dose dependent manner. BN caused translocation of protein kinase C from the cytosol to the membrane and the translocation caused by BN was reversed by (D-Phe6)BN6-13methylester. BN stimulated arachidonic acid release and the increase caused by BN was reversed by (D-Phe6)BN6-13methylester. Using a clonogenic assay, BN stimulated the growth of NCI-H720 cells, and the number of colonies was reduced using (D-Phe6)BN6-13methylester. These data suggest that GRP receptors that are present in lung carcinoid and NSCLC cells may regulate proliferation.
Moody
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TW
Biomarkers and Prevention Research Branch, National Cancer Institute, Rockville, Maryland 20876, USA.
Zia
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Venugopal
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Fagarasan
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Oie
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Hu
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D016718:Arachidonic Acid / Q000378:metabolism; D001839:Bombesin / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002276:Carcinoid Tumor / Q000737:chemistry / Q000473:pathology; D018287:Carcinoma, Large Cell / Q000737:chemistry / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000737:chemistry* / Q000473:pathology; D018288:Carcinoma, Small Cell / Q000737:chemistry / Q000473:pathology; D019886:Gastrin-Releasing Peptide; D006801:Humans; D008175:Lung Neoplasms / Q000737:chemistry* / Q000473:pathology; D009363:Neoplasm Proteins / Q000032:analysis*; D010455:Peptides / Q000378:metabolism; D018004:Receptors, Bombesin / Q000032:analysis*
D009363:Neoplasm Proteins; D010455:Peptides; D018004:Receptors, Bombesin; D016718:Arachidonic Acid; D019886:Gastrin-Releasing Peptide; D001839:Bombesin; D002118:Calcium