Beta-Adrenergic Receptors Regulating Growth and Replication of Breast Cancer Cells: Basic and Therapeutic Implications
Abstract
This study explores beta-adrenoceptors on breast cancer cells as a therapeutic target. MDA-MB-231 human breast cancer cells express high beta2-adrenoceptor levels. Receptor stimulation by isoproterenol evoked immediate reductions in DNA synthesis which were blocked completely by propranolol and were of the same magnitude as effects elicited by high concentrations of 8-Br-cAMP. Isoproterenol induced inhibition of DNA synthesis was maintained throughout several days of exposure, resulting in a decrement in total cell number, and the effects were augmented by cotreatment with dexamethasone; an even greater effect was seen when cAMP breakdown was inhibited by theophylline, with or without addition of isoproterenol. Despite the persistent effect of isoproterenol, receptor downregulation was evident within 1h and over 90% of the receptors were lost within 24h. Receptor downregulation was paralleled by homologous desensitization of the adenylyl cyclase response to beta-adrenoceptor stimulation. These results indicate that beta-adrenoceptors are effectively linked to the termination of cell replication in MDA-MB-231 cells and that activation of only a small number of receptors is sufficient for the effect. Strategies focusing on cell surface receptors may combat cancers that are unresponsive to hormonal agents, or that have developed multidrug resistance.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 1999
- Accession Number
- ADB258194
Entities
People
- Theodore A. Slotkin
Organizations
- Duke University Hospital