title: Parathyroid hormone-related protein, an autocrine regulatory factor in alveolar epithelial cells.
abstract: Alveolar epithelial cells in vivo, primary cultures of adult rat type II cells, and human A549 alveolar carcinoma cells express parathyroid hormone-related protein (PTHrP). Here we demonstrated that type II cells and A549 cells also express the PTHrP receptor and that they exhibit differentiation-related responses to the amino-terminal PTHrP fragment, PTHrP-(1-34). PTHrP receptor expression in A549 cells was shown by detection of a 0.3-kb reverse transcriptase polymerase chain reaction product formed by primers specific for PTHrP receptor. In situ hybridization studies localized the site of production of PTHrP and PTHrP receptor mRNA in rat lung cells with morphology and location typical of type II cells. Primary cultures of such type II cells also expressed PTHrP receptor mRNA. Incubation with PTHrP-(1-34) stimulated disaturated phosphatidylcholine (DSPC) synthesis in A549 cells and increased the release of newly synthesized DSPC by cultured type II cells and A549 cells. In addition, PTHrP-(1-34) increased the number of lamellar bodies per type II cell and increased their expression of alkaline phosphatase in a dose-dependent manner. Thus PTHrP-(1-34) promoted a differentiated type II cell phenotype. Since cultured type II cells, alveolar epithelial cells in vivo, and A549 cells express PTHrP and the PTHrP receptor, PTHrP-(1-34) may be an autocrine regulatory factor in type II cells and lung cancer cells.
authors.affiliation: Department of Veterans Affairs Medical Center, 92161-5085, San Diego, California 92103-8770, USA.
authors.forename: R H
authors.initials: RH
authors.lastname: Hastings
authors.forename: D
authors.initials: D
authors.lastname: Summers-Torres
authors.forename: T C
authors.initials: TC
authors.lastname: Cheung
authors.forename: L S
authors.initials: LS
authors.lastname: Ditmer
authors.forename: E M
authors.initials: EM
authors.lastname: Petrin
authors.forename: D W
authors.initials: DW
authors.lastname: Burton
authors.forename: R G
authors.initials: RG
authors.lastname: Spragg
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.forename: L J
authors.initials: LJ
authors.lastname: Deftos
mesh_terms: D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002478:Cells, Cultured; D017931:DNA Primers; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D017403:In Situ Hybridization; D008175:Lung Neoplasms; D008297:Male; D008969:Molecular Sequence Data; D015388:Organelles / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D010281:Parathyroid Hormone / Q000494:pharmacology; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D011506:Proteins / Q000494:pharmacology*; D011650:Pulmonary Alveoli / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044168:Receptor, Parathyroid Hormone, Type 1; D018016:Receptors, Parathyroid Hormone / Q000096:biosynthesis*; D019379:Teriparatide; D014407:Tumor Cells, Cultured
chemical_list: D017931:DNA Primers; C470121:PTHLH protein, human; D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments; D011506:Proteins; D044168:Receptor, Parathyroid Hormone, Type 1; D018016:Receptors, Parathyroid Hormone; D019379:Teriparatide