ASSOCIATION OF INCREASED CYCLIC ADENOSINE 3'-5'-MONOPHOSPHATE CONTENT IN CULTURED HUMAN-BREAST CANCER-CELLS AND RELEASE OF HYDROLYTIC ENZYMES AND BONE-RESORBING ACTIVITY

  • 1 January 1983
    • journal article
    • research article
    • Vol. 43  (12) , 5792-5794
Abstract
The established human breast cancer cell line MCF-7 resorbs bone directly in vitro independently of viable endogenous bone cells, and this resorption of bone is closely correlated with the release of hydrolytic enzymes by the cultured tumor cells. In this study the effects were examined of a number of drugs which increase the intracellular cAMP content on the release of hydrolytic enzymes by the tumor cells and their capacity to resorb bone. When MCF-7 cultures were treated with cholera toxin (0.05 to 5 .mu.g/ml), a potent adenylate cyclase inducer, mineral-releasing, lysosomal enzyme and collagenolytic activities increased more than 2-fold in the cell culture medium. Prostaglandin E1 (0.1 .mu.M), 8-bromo-cAMP (10 mM), and isobutylmethylxanthine (30 .mu.M) caused similar effects. Adenylate cyclase activation and increases in cAMP content in the tumor cells caused the release of lysosomal enzymes and collagenolytic activity and caused the resorption of bone. Colchicine, a drug which inhibits microtubule assembly, also increased hydrolytic enzyme release and release of bone-resorbing activity. Direct measurements of cAMP were made in MCF-7 cells 3 h after treatment with colchicine (10 .mu.M) as well as MCF-7 cells treated with prostaglandin E1, cholera toxin and isobutylmethylxanthine. MCF-7 cells showed a 2-fold increase in cAMP content after treatment with all of these agents, although there was no similar increase in mouse fibroblast 3T3 cells which do not produce bone-resorbing activity under these conditions. Increases in cAMP concentrations in human breast cancer cells apparently lead to release of hydrolytic enzymes and resorption of bone.

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