{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T19:46:19Z","timestamp":1790970379027,"version":"4.1.0"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[1997,8,1]],"date-time":"1997-08-01T00:00:00Z","timestamp":870393600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1997,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Bombesin-like peptides (BLPs) are important regulators of lung development and may also act as autocrine growth factors in lung tumors. We have previously demonstrated expression of mRNA for the three BLP receptor subtypes (neuromedin B [NMB] receptor, gastrin-releasing peptide [GRP] receptor, and bombesin receptor subtype 3 [BRS-3]) in human non-small cell lung carcinoma (NSCLC) cell lines and bronchial biopsies using the reverse transcription-polymerase chain reaction (RT-PCR; DeMichele, et al. Am. J. Respir. Cell Mol. Biol. 1994;11:66\u201374). We have also previously found that growth responses to BLPs could be elicited in some, but not all, cultures of human bronchial epithelial (HBE) cells (Siegfried, et al. Anat. Rec. 1993;236:241\u2013247). In this report, we utilized RT-PCR to demonstrate mRNA expression of BLP receptor subtypes in cultured HBE cells and also assessed the response of these cultures to BLPs in proliferation assays. The pattern of mRNA expression was correlated with proliferative response, and the results were also analyzed in relation to smoking history and pulmonary function of the subjects studied. Our results suggest that expression of mRNA for the GRP receptor is associated with a long smoking history ( &amp;gt; 25 pack-years [PY], p = 0.02). This association was related to past tobacco exposure, regardless of whether the subjects were still active smokers at the time of tissue procurement. Responsiveness to GRP and NMB in proliferation assays was also found only in those HBE cultures with expression of mRNA for at least one of the known receptors for BLPs, and there was a significant association between expression of mRNA for the GRP receptor and proliferative response to both GRP and NMB (p = 0.048). HBE cultures from subjects with a greater than 25 PY smoking history were also more likely to respond to BLPs in the proliferation assays than cells from subjects with less than a 25 PY history (10 of 16 versus 1 of 7, p = 0.06). Cultures of HBE cells from four of the five subjects with severe obstructive lung disease gave a positive response to GRP and NMB in proliferation assays, compared to five of fifteen without severe obstructive lung disease, but this difference was not significant (p = 0.13). These results suggest there is an increased likelihood of expression of the GRP receptor mRNA in the respiratory epithelium of some individuals with a history of prolonged tobacco exposure, and that expression of the GRP receptor mRNA is accompanied by responsiveness to the mitogenic effects of BLPs. These effects appear to persist after smoking cessation.<\/jats:p>","DOI":"10.1164\/ajrccm.156.2.9608047","type":"journal-article","created":{"date-parts":[[2013,4,4]],"date-time":"2013-04-04T13:25:36Z","timestamp":1365081936000},"page":"358-366","source":"Crossref","is-referenced-by-count":39,"title":["Expression of mRNA for Gastrin-Releasing Peptide Receptor by Human Bronchial Epithelial Cells"],"prefix":"10.1093","volume":"156","author":[{"given":"JILL M.","family":"SIEGFRIED","sequence":"first","affiliation":[{"name":"Departments of Pharmacology and Medicine and University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Biology, Carlow College, Pittsburgh, Pennsylvania; and Department of Biochemistry and Molecular Biology, Louisiana State University Medical Center, Stanley S. Scott Cancer Center, New Orleans, Louisiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MARY ANN A.","family":"DeMICHELE","sequence":"additional","affiliation":[{"name":"Departments of Pharmacology and Medicine and University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Biology, Carlow College, Pittsburgh, Pennsylvania; and Department of Biochemistry and Molecular Biology, Louisiana State University Medical Center, Stanley S. Scott Cancer Center, New Orleans, Louisiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JAY D.","family":"HUNT","sequence":"additional","affiliation":[{"name":"Departments of Pharmacology and Medicine and University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Biology, Carlow College, Pittsburgh, Pennsylvania; and Department of Biochemistry and Molecular Biology, Louisiana State University Medical Center, Stanley S. Scott Cancer Center, New Orleans, Louisiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"AUTUMN GAITHER","family":"DAVIS","sequence":"additional","affiliation":[{"name":"Departments of Pharmacology and Medicine and University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Biology, Carlow College, Pittsburgh, Pennsylvania; and Department of Biochemistry and Molecular Biology, Louisiana State University Medical Center, Stanley S. Scott Cancer Center, New Orleans, Louisiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"KUNWAR P.","family":"VOHRA","sequence":"additional","affiliation":[{"name":"Departments of Pharmacology and Medicine and University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Biology, Carlow College, Pittsburgh, Pennsylvania; and Department of Biochemistry and Molecular Biology, Louisiana State University Medical Center, Stanley S. Scott Cancer Center, New Orleans, Louisiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JOSEPH M.","family":"PILEWSKI","sequence":"additional","affiliation":[{"name":"Departments of Pharmacology and Medicine and University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Biology, Carlow College, Pittsburgh, Pennsylvania; and Department of Biochemistry and Molecular Biology, Louisiana State University Medical Center, Stanley S. Scott Cancer Center, New Orleans, Louisiana"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[1997,8,1]]},"reference":[{"key":"2026032709231358000_B1","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1002\/ar.1092270309","article-title":"Dynamics of neuroepithelial body (NEB) formation in developing hamster lung: light microscopic autoradiography after 3H-thymidine labeling in vivo.","volume":"227","author":"Hoyt","year":"1990","journal-title":"Anat. Rec"},{"key":"2026032709231358000_B2","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1165\/ajrcmb.14.5.8624244","article-title":"Roles of bombesin-like peptides in lung development and lung injury.","volume":"14","author":"Spindel","year":"1996","journal-title":"Am. J. Respir. Cell Mol. Biol"},{"key":"2026032709231358000_B3","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1002\/ar.1092360106","article-title":"Neuroepithelial bodies and growth of the airway epithelium in developing hamster lung.","volume":"236","author":"Hoyt","year":"1993","journal-title":"Anat. Rec"},{"key":"2026032709231358000_B4","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1165\/ajrcmb\/3.3.199","article-title":"Bombesin increases fetal lung growth and maturation in utero and in organ culture.","volume":"3","author":"Sunday","year":"1990","journal-title":"Am. J. Respir. Cell Mol. Biol"},{"key":"2026032709231358000_B5","first-page":"821","article-title":"Selective stimulation of small cell lung cancer clonal growth by bombesin and gastrin-releasing peptide.","volume":"47","author":"Carney","year":"1987","journal-title":"Cancer Res"},{"key":"2026032709231358000_B6","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1038\/316823a0","article-title":"Bombesin-like peptides can function as autocrine growth factors in human small-cell lung cancer.","volume":"316","author":"Cuttitta","year":"1985","journal-title":"Nature (Lond.)"},{"key":"2026032709231358000_B7","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/0024-3205(85)90413-8","article-title":"High affinity receptors for bombesin\/GRP-like peptides on human small cell lung cancer.","volume":"37","author":"Moody","year":"1985","journal-title":"Life Sci"},{"key":"2026032709231358000_B8","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/0014-4827(84)90466-X","article-title":"Bombesin and C-terminal tetradecapeptide of gastrin-releasing peptide are growth factors for normal bronchial epithelial cells.","volume":"153","author":"Willey","year":"1984","journal-title":"Exp. Cell Res"},{"key":"2026032709231358000_B9","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1002\/ar.1092360129","article-title":"Effects of bombesin and gastrin-releasing peptide on human bronchial epithelial cells from a series of donors: individual variation and modulation by bombesin analogs.","volume":"236","author":"Siegfried","year":"1993","journal-title":"Anat. Rec"},{"key":"2026032709231358000_B10","doi-asserted-by":"crossref","first-page":"8596","DOI":"10.1016\/S0021-9258(17)37236-8","article-title":"Production of gastrin-releasing peptide by a non-small cell lung carcinoma cell line adapted to serum-free and growth factor-free conditions.","volume":"269","author":"Siegfried","year":"1994","journal-title":"J. Biol. Chem"},{"key":"2026032709231358000_B11","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1073\/pnas.88.2.395","article-title":"Molecular cloning of the bombesin\/gastrin-releasing peptide receptor from Swiss 3T3 cells.","volume":"88","author":"Battey","year":"1991","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2026032709231358000_B12","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/0896-6273(91)90250-4","article-title":"cDNA cloning, characterization and brian region-specific expression of a neuromedin-B preferring bombesin receptor.","volume":"6","author":"Wada","year":"1991","journal-title":"Neuron"},{"key":"2026032709231358000_B13","doi-asserted-by":"crossref","first-page":"5979","DOI":"10.1016\/S0021-9258(18)53415-3","article-title":"A novel bombesin receptor subtype selectively expressed in testis and lung carcinoma cells.","volume":"268","author":"Fathi","year":"1993","journal-title":"J. Biol. Chem"},{"key":"2026032709231358000_B14","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1165\/ajrcmb.11.1.8018339","article-title":"Expression of mRNA for three bombesin receptor subtypes in human bronchial epithelial cells.","volume":"11","author":"DeMichele","year":"1994","journal-title":"Am. J. Respir. Cell Mol. Biol"},{"key":"2026032709231358000_B15","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1165\/ajrcmb.14.5.8624245","article-title":"Expression of gastrin-releasing peptide receptor gene in developing lung.","volume":"14","author":"Wang","year":"1996","journal-title":"Am. J. Respir. Cell Mol. Biol"},{"key":"2026032709231358000_B16","first-page":"5205","article-title":"Production of neutromedin B and neutromedin B gene expression in human lung tumor cell lines.","volume":"51","author":"Cardona","year":"1991","journal-title":"Cancer Res"},{"key":"2026032709231358000_B17"},{"key":"2026032709231358000_B18","doi-asserted-by":"crossref","first-page":"18771","DOI":"10.1016\/S0021-9258(18)55129-2","article-title":"Two distinct bombesin receptor subtypes are expressed and functional in human lung carcinoma cells.","volume":"266","author":"Corjay","year":"1991","journal-title":"J. Biol. Chem"},{"key":"2026032709231358000_B19","first-page":"42","article-title":"Bombesin-like peptide receptor expression in human lung cancer cells.","volume":"36","author":"Toi","year":"1995","journal-title":"Proc. Am. Assoc. Cancer Res"},{"key":"2026032709231358000_B20"},{"key":"2026032709231358000_B21","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1172\/JCI114273","article-title":"Increased levels of bombesin-like peptides in the lower respiratory tract of asymptomatic cigarette smokers.","volume":"84","author":"Aguayo","year":"1989","journal-title":"J. Clin. Invest"},{"key":"2026032709231358000_B22","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1002\/path.1711570207","article-title":"Pulmonary endocrine cells in chronic bronchitis and emphysema.","volume":"157","author":"Gosney","year":"1989","journal-title":"J. Pathol"},{"key":"2026032709231358000_B23","first-page":"1853","article-title":"Expression of the gastrin-releasing peptide receptor confers a growth response to bombesin in immortalized human bronchial epithelial cells.","volume":"45","author":"Moustafa","year":"1995","journal-title":"Cancer Res."},{"key":"2026032709231358000_B24","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1093\/carcin\/5.10.1317","article-title":"Cytotoxicity of chemical carcinogens towards human bronchial epithelial cells evaluated in a clonal assay.","volume":"5","author":"Siegfried","year":"1984","journal-title":"Carcinogenesis Lond"},{"key":"2026032709231358000_B25"},{"key":"2026032709231358000_B26","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/0196-9781(94)00173-1","article-title":"Bombesin stimulates c-fos and c-jun mRNAs in small cell lung cancer cells.","volume":"16","author":"Draoui","year":"1995","journal-title":"Peptides"},{"key":"2026032709231358000_B27","doi-asserted-by":"crossref","first-page":"4357","DOI":"10.1073\/pnas.92.10.4357","article-title":"Bombesin and [Leu8]- phyllolitorin promote fetal mouse lung branching morphogenesis via a receptor-mediated mechanism.","volume":"92","author":"King","year":"1995","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2026032709231358000_B28","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1038\/bjc.1991.301","article-title":"Neuroendocrine differentiation and clinical behaviour in non-small cell lung tumours.","volume":"64","author":"Sundaresan","year":"1991","journal-title":"Br. J. Cancer"},{"key":"2026032709231358000_B29","first-page":"20","article-title":"Atypical endocrine tumors of the lung.","volume":"105","author":"McDowell","year":"1981","journal-title":"Arch. Pathol. Lab. Med"},{"key":"2026032709231358000_B30","doi-asserted-by":"crossref","first-page":"6523","DOI":"10.1073\/pnas.85.17.6523","article-title":"v-Ha-ras oncogene insertion: a model for tumor progression of human small cell lung cancer.","volume":"85","author":"Mabry","year":"1988","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2026032709231358000_B31"},{"key":"2026032709231358000_B32"},{"key":"2026032709231358000_B33","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1203\/00006450-198206000-00009","article-title":"Pulmonary neuroendocrine cells in bronchopulmonary dysplasia and hyaline membrane disease.","volume":"16","author":"Johnson","year":"1982","journal-title":"Pediatr. Res"},{"key":"2026032709231358000_B34","doi-asserted-by":"crossref","first-page":"1692","DOI":"10.1164\/ajrccm.149.6.7911710","article-title":"Determinants of susceptibility to cigarette smoke: potential roles for neuroendocrine cells and neuropeptides in airway inflammation, airway wall remodeling, and chronic airflow obstruction.","volume":"149","author":"Aguayo","year":"1994","journal-title":"Am. J. Respir. Crit. Care Med"},{"key":"2026032709231358000_B35","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1172\/JCI114782","article-title":"Increased pulmonary neuroendocrine cells with bombesin like immunoreactivity in adult patients with eosinophilic granuloma.","volume":"86","author":"Aguayo","year":"1993","journal-title":"J. Clin. Invest"},{"key":"2026032709231358000_B36","first-page":"195","article-title":"Bombesin\/gastrin releasing peptide levels of peripheral mononuclear cells, monocytes and alveolar macrophages in chronic bronchitis.","volume":"14","author":"Meloni","year":"1992","journal-title":"Int. J. Tiss. Res"},{"key":"2026032709231358000_B37","first-page":"1613","article-title":"Receptor subtype expression and responsiveness to bombesin in cultured human bronchial epithelial cells.","volume":"54","author":"Frankel","year":"1994","journal-title":"Cancer Res"}],"container-title":["American Journal of Respiratory and Critical Care Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/156\/2\/358\/67448703\/ajrccm_156_2_358.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/156\/2\/358\/67448703\/ajrccm_156_2_358.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T13:23:21Z","timestamp":1774617801000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ajrccm\/article\/156\/2\/358\/8530874"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1997,8,1]]},"references-count":37,"journal-issue":{"issue":"2","published-online":{"date-parts":[[1997,8,1]]},"published-print":{"date-parts":[[1997,8,1]]}},"URL":"https:\/\/doi.org\/10.1164\/ajrccm.156.2.9608047","relation":{},"ISSN":["1073-449X","1535-4970"],"issn-type":[{"value":"1073-449X","type":"print"},{"value":"1535-4970","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[1997,8]]},"published":{"date-parts":[[1997,8,1]]}}}