Expression of mRNA for gastrin-releasing peptide receptor by human bronchial epithelial cells. Association with prolonged tobacco exposure and responsiveness to bombesin-like peptides.

Abstract

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; 11:66-74). 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; 236:241-247). 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 (> 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.