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 μM isoproterenol compared to non-tumorigenic C10 cells derived from normal mouse lung epithelium. Iodocyanopindolol binding studies indicated that both neoplastic lines contained fewer β-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 μM 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.
Bibliographical noteFunding Information:
We would like to thank Dr. G.L. Johnson (NationaJle wish Centerf or Immunologya nd Respiratory Medicine, Denver) for helpful commentso n this manuscriptW. e are grateful to Ms. S. Leah Butler for excellentt echnical assistance.T his work was supported by USPHS Grant ES02370.
- GTP-binding proteins
- adenylate cyclase
- beta-adrenergic receptor
- growth regulation
- lung epithelial cell lines