Estrogen deprivation causes estradiol hypersensitivity in human breast cancer cells

Shigeru Masamura, Steven J. Santner, Daniel F. Heitjan, Richard J. Santen

Research output: Contribution to journalArticle

278 Citations (Scopus)

Abstract

Genetic and environmental factors can modulate the level of sensitivity to various hormones, including estrogens. Enhanced sensitivity to estradiol (E2) has been demonstrated in several biological conditions, such as in sheep during the nonbreeding season, in untreated patients with Turner’s syndrome, and in the prepubertal state in normal girls. We postulated that secondary responses to hormonal therapy in patients with breast cancer could also result from enhanced E2 sensitivity, developing as an adaptive mechanism to E2 deprivation. The present study used the MCF-7 human breast cancer cell line as a model system to test the concept that enhanced sensitivity to E2 may occur as a result of adaptation to low E2 levels. After depriving MCF-7 cells of estrogens in tissue culture medium for periods of 1-6 months, we established conditions under which replication could be stimulated maximally by 10-14-10-15 mol/L E2. In contrast, wild-type cells not exposed to estrogen deprivation required 10-10 mol/L E2 to grow at the same rate. Further, the concentration of the antiestrogen, ICI 164384, needed to inhibit growth by 50% in estrogen-deprived cells was much lower than that required in wild-type cells (i.e. 10-15 vs. 10-9 mol/L). Nude mice implanted with these estrogen-deprived cells demonstrated an earlier appearance of palpable tumors in response to E2 than animals bearing wild-type cells. Reexposure to 10-10-10-9 mol/L E2, either in vivo or in vitro, returned these cells to the level of estrogen sensitivity observed in wild-type cells. Taken together, these observations suggest that breast cancer cells can adapt to low levels of estrogens by enhancing their sensitivity to E2.

Original languageEnglish (US)
Pages (from-to)2918-2925
Number of pages8
JournalJournal of Clinical Endocrinology and Metabolism
Volume80
Issue number10
DOIs
StatePublished - Jan 1 1995

Fingerprint

Estradiol
Hypersensitivity
Estrogens
Cells
Breast Neoplasms
Bearings (structural)
Tissue culture
Estrogen Receptor Modulators
Turner Syndrome
Wild Animals
MCF-7 Cells
Culture Media
Tumors
Nude Mice
Animals
Sheep
Hormones
Cell Line
Growth
Neoplasms

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Estrogen deprivation causes estradiol hypersensitivity in human breast cancer cells. / Masamura, Shigeru; Santner, Steven J.; Heitjan, Daniel F.; Santen, Richard J.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 80, No. 10, 01.01.1995, p. 2918-2925.

Research output: Contribution to journalArticle

Masamura, Shigeru ; Santner, Steven J. ; Heitjan, Daniel F. ; Santen, Richard J. / Estrogen deprivation causes estradiol hypersensitivity in human breast cancer cells. In: Journal of Clinical Endocrinology and Metabolism. 1995 ; Vol. 80, No. 10. pp. 2918-2925.
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