Differential responsiveness to agents which stimulate cAMP production in normal versus neoplastic mouse lung epithelial cells.
We examined the responsiveness of normal and neoplastic lung cells to agents which stimulate cAMP production. While their basal cAMP levels were similar, spontaneous in vitro transformant E9 cells and tumor-derived PCC4 cells produced much less cAMP in response to 1 microM isoproterenol compared to non-tumorigenic C10 cells derived from normal mouse lung epithelium. Iodocyanopindolol binding studies indicated that both neoplastic lines contained fewer beta-adrenergic receptors than normal C10 cells. When receptors were bypassed via treatment with 10 pM cholera toxin, the pattern of cAMP-responsiveness was reversed; both neoplastic cell lines produced more cAMP than C10 cells. Direct stimulation of adenylate cyclase with 100 microM forskolin greatly increased cAMP concentrations in all three cell lines. These anomalies at both the receptor and G-protein levels in neoplastic lung epithelial cells may contribute to their deregulated growth.
Lange-Carter
C A
CA
Molecular and Environmental Toxicology Program, School of Pharmacy, University of Colorado, Boulder 80309-0297.
Droms
K A
KA
Vuillequez
J J
JJ
Malkinson
A M
AM
D000262:Adenylyl Cyclases / Q000187:drug effects; D000818:Animals; D002460:Cell Line; D002772:Cholera Toxin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis*; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D008168:Lung / Q000166:cytology / Q000378:metabolism*; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D011943:Receptors, Adrenergic, beta / Q000032:analysis; D015398:Signal Transduction; D013268:Stimulation, Chemical; D014407:Tumor Cells, Cultured / Q000187:drug effects
D011943:Receptors, Adrenergic, beta; D005576:Colforsin; D002772:Cholera Toxin; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D007545:Isoproterenol