title: The effects of prostaglandin E2, parathyroid hormone, and epidermal growth factor on mitogenesis, signaling, and primary response genes in UMR 106-01 osteoblast-like cells.
abstract: Prostaglandin E2 (PGE2), PTH, and epidermal growth factor (EGF) are potent regulators of osteoblast proliferation. In UMR 106-01 rat osteosarcoma cells with osteoblast-like features, PGE2 and PTH inhibit, while EGF stimulates, mitogenesis. Both PGE2 and PTH increase intracellular cAMP levels, cytosolic calcium, and inositol phosphate turnover. In a variety of cell types, EGF mediates its effects in part via activation of receptor protein-tyrosine kinase and other protein kinases, such as protein kinase-C. The nuclear mechanisms of PGE2, PTH, and EGF regulation of osteoblast proliferation are unknown. Accordingly, we have examined the effects of these agents on mitogenesis, second messenger generation, and primary response genes, which may link second messenger activation to subsequent alterations in gene expression. Northern blot analysis of mRNA from UMR 106-01 cells treated for 3 h with 2 microM PGE2, 10 nM PTH, or 10 ng/ml EGF in the presence of cycloheximide demonstrated that all three agents induced the expression of c-fos and c-jun mRNA. In contrast, only EGF stimulated cellular proliferation and induced Egr-1 mRNA. Also, unlike PGE2 and PTH, EGF did not increase intracellular cAMP levels. c-fos mRNA was induced by treatment with 50 ng/ml tetradecanoyl phorbol acetate or by 40 ng/ml forskolin, while induction of Egr-1 mRNA was stimulated by treatment with tetradecanoyl phorbol acetate, but not forskolin. Thus, EGF signal transduction differs from that of PGE2 and PTH in UMR 106-01 osteoblast-like cells, in that EGF does not stimulate the protein kinase-A second messenger system, but causes activation of Egr-1, a primary response gene that may play a role in the mitogenic effect of EGF.
authors.affiliation: Geriatric Research, Education, and Clinical Center, Wadsworth Veterans Administration Medical Center, Los Angeles, California 90073.
authors.forename: M A
authors.initials: MA
authors.lastname: Fang
authors.forename: D A
authors.initials: DA
authors.lastname: Kujubu
authors.forename: T J
authors.initials: TJ
authors.lastname: Hahn
mesh_terms: D000818:Animals; D001859:Bone Neoplasms; D002118:Calcium / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000235:genetics; D015232:Dinoprostone / Q000494:pharmacology*; D051766:Early Growth Response Protein 1; D004789:Enzyme Activation; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000502:physiology; D016762:Genes, fos / Q000235:genetics*; D016758:Genes, jun / Q000235:genetics*; D017874:Immediate-Early Proteins; D007295:Inositol Phosphates / Q000378:metabolism; D008938:Mitosis / Q000187:drug effects* / Q000502:physiology; D010006:Osteoblasts / Q000378:metabolism / Q000473:pathology* / Q000502:physiology; D012516:Osteosarcoma; D010281:Parathyroid Hormone / Q000494:pharmacology*; D011494:Protein Kinases / Q000378:metabolism / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics; D014316:Tritium; D014407:Tumor Cells, Cultured; D016335:Zinc Fingers
chemical_list: D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D017874:Immediate-Early Proteins; D007295:Inositol Phosphates; D010281:Parathyroid Hormone; D012333:RNA, Messenger; D014157:Transcription Factors; D014316:Tritium; D005576:Colforsin; D004815:Epidermal Growth Factor; D003513:Cycloheximide; D000242:Cyclic AMP; D011494:Protein Kinases; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium; D013936:Thymidine