Direct inhibition of growth and antagonism of insulin action by glucocorticoids in human breast cancer cells in culture

C. Kent Osborne, Marie E. Monaco, Kahn C. Ronald, Karen Huff, Diane Bronzert, Marc E. Lippman

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56 Scopus citations

Abstract

We have examined the interaction of dexamethasone with the ZR75-1 human breast cancer cell line to determine if glucocorticoids might directly inhibit growth of breast cancer cells. Growth of these cells in serum-free medium was stimulated significantly by physiological concentrations of insulin (0.1 to 1.0 nM). Pharmacological concentrations of dexamethasone (10 nM) reduced cell number below that found in controls and nearly abolished the effect of insulin after several days in culture. Thymidine and uridine, but not leucine, incorporation into macromolecules or acetate incorporation into fatty acids were similarly inhibited by dexamethasone in the presence or absence of insulin. Dexamethasone did not inhibit insulin effects by altering insulin receptor affinity or concentration, as determined by Scatchard analyses of insulin binding. Net thymidine uptake into the trichloroacetic acid-soluble fraction of the cell was stimulated by insulin and inhibited by dexamethasone. Dexamethasone also inhibited thymidine kinase activity in both control and insulin-stimulated cells. These data suggest multiple potential sites of glucocorticoid action that directly oppose the effects of insulin. They also suggest that glucocorticoids have a direct inhibitory effect on proliferation of human breast cancer cells, which may help explain breast tumor regression following pharmacological glucocorticoid therapy.

Original languageEnglish (US)
Pages (from-to)2422-2428
Number of pages7
JournalCancer Research
Volume39
StatePublished - Jan 1 1979

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Osborne, C. K., Monaco, M. E., Ronald, K. C., Huff, K., Bronzert, D., & Lippman, M. E. (1979). Direct inhibition of growth and antagonism of insulin action by glucocorticoids in human breast cancer cells in culture. Cancer Research, 39, 2422-2428.