HORMONE DEPENDENCE OF BREAST-CANCER CELLS AND THE EFFECTS OF TAMOXIFEN AND ESTROGEN - P-31 NMR-STUDIES

Many breast tumors appear to progress from estrogen-dependent growth t o a more malignant phenotype characterized by estrogen-independent gro wth, antiestrogen resistance, and a high metastatic potential. Utilizi ng P-31 NMR spectroscopy on human breast cancer cells growing in vitro , we have investigated the effects of 17 beta-estradiol and tamoxifen on the metabolic/bioenergetic spectra of a series of human breast canc er cells that vary in their estrogen and antiestrogen responsiveness. A comparison of baseline spectra associates higher levels of phosphodi esters and UDP-glucosides (e.g. UDP-glucose, UDP-N-acetylglucosamine), and lower phosphocholine/glycerylphosphocholine and phosphocholine/ph osphoethanolamine ratios, with the acquisition of estrogen-independent growth in estrogen receptor expressing cells. No metabolic changes ar e clearly associated with the metastatic phenotype. Whilst estrogen tr eatment produces no consistently significant spectral changes in any o f the cell lines, the estrogen-independent and estrogen-responsive MCF 7/MIII cell line responds to tamoxifen treatment by significantly incr easing all spectral resonances 30%-40% above baseline values. This may reflect a tamoxifen-induced change to a more differentiated or apopto tic phenotype, or an attempt by the cells to reverse the inhibitory ef fects of the drug. The ability to detect metabolic changes in response to tamoxifen by NMR spectroscopy may provide a novel means to identif y those tumors that are responsive to antiestrogen therapy.