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Hormone dependence of breast cancer cells and the effects of tamoxifen and estrogen:31P NMR studies

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Abstract

Many breast tumors appear to progress from estrogen-dependent growth to a more malignant phenotype characterized by estrogen-independent growth, antiestrogen resistance, and a high metastatic potential. Utilizing31P NMR spectroscopy on human breast cancer cells growingin vitro, we have investigated the effects of 17β-estradiol and tamoxifen on the metabolic/bioenergetic spectra of a series of human breast cancer cells that vary in their estrogen and antiestrogen responsiveness. A comparison of baseline spectra associates higher levels of phosphodiesters and UDP-glucosides (e.g. UDP-glucose, UDP-N-acetylglucosamine), and lower phosphocholine/glycerylphosphocholine and phosphocholine/phosphoethanolamine ratios, with the acquisition of estrogen-independent growth in estrogen receptor expressing cells. No metabolic changes are clearly associated with the metastatic phenotype. Whilst estrogen treatment produces no consistently significant spectral changes in any of the cell lines, the estrogen-independent and estrogen-responsive MCF7/MIII cell line responds to tamoxifen treatment by significantly increasing all spectral resonances 30%-40% above baseline values. This may reflect a tamoxifen-induced change to a more differentiated or apoptotic phenotype, or an attempt by the cells to reverse the inhibitory effects of the drug. The ability to detect metabolic changes in response to tamoxifen by NMR spectroscopy may provide a novel means to identify those tumors that are responsive to antiestrogen therapy.

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Abbreviations

CCS-IMEM:

steroid-deprived Improved Minimal Essential Medium

E2:

17β-estradiol

ER:

estrogen receptor

Pi :

inorganic phosphate

GPE:

glyceryl-phosphoethanolamine

GPC:

glyceryl-phosphocholine

PC:

phosphocholine

PE:

phosphoethanolamine

PDE:

phosphodiesters

PME:

phosphomonoesters

TAM:

tamoxifen (trans-1-(4-β-dimethylaminoethoxyphenyl)-1,2-diphenylbut-1-ene)

UDPG:

uridine diphosphoglycoside

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Author notes

  1. Jesús Ruiz-Cabello

    Present address: Instituto Pluridisciplinar de la Universidad Complutense de Madrid, Avenida Juan XXIII, 28040, Madrid, Spain

Authors and Affiliations

  1. Lombardi Cancer Research Center Shady Grove Laboratories, 4 Research Court, 20850, Rockville, MD, USA

    Jesús Ruiz-Cabello, Kirsten Berghmans & Jack S. Cohen

  2. Ichilov Hospital, 6 Weizmann Street, Tel Aviv, Israel

    Ofer Kaplan

  3. Vincent T. Lombardi Cancer Research Center, Georgetown University Medical School, 3800 Reservoir Road NW, 20007, Washington, DC, USA

    Marc E. Lippman & Robert Clarke

  4. Department of Physiology & Biophysics, Georgetown University Medical School, 3800 Reservoir Road NW, 20007, Washington, DC, USA

    Robert Clarke

Authors
  1. Jesús Ruiz-Cabello
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  3. Ofer Kaplan
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  4. Marc E. Lippman
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  5. Robert Clarke
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  6. Jack S. Cohen
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Ruiz-Cabello, J., Berghmans, K., Kaplan, O. et al. Hormone dependence of breast cancer cells and the effects of tamoxifen and estrogen:31P NMR studies. Breast Cancer Res Tr 33, 209–217 (1995). https://doi.org/10.1007/BF00665945

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