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MCF7/LCC2: A 4-Hydroxytamoxifen Resistant Human Breast Cancer Variant That Retains Sensitivity to the Steroidal Antiestrogen ICI 182,780

Nils Brünner, Thomas L. Frandsen, Claus Holst-Hansen, Mian Bei, Erik W. Thompson, Alan E. Wakeling, Marc E. Lippman and Robert Clarke
Nils Brünner
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Thomas L. Frandsen
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Claus Holst-Hansen
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Mian Bei
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Erik W. Thompson
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Alan E. Wakeling
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Marc E. Lippman
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Robert Clarke
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DOI:  Published July 1993
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Abstract

The development of resistance to the antiestrogen tamoxifen occurs in a high percentage of initially responsive patients. We have developed a new model in which to investigate acquired resistance to triphenylethylenes. A stepwise in vitro selection of the hormone-independent human breast cancer variant MCF-7/LCC1 against 4-hydroxytamoxifen produced a stable resistant population designated MCF7/LCC2. MCF7/LCC2 cells retain levels of estrogen receptor expression comparable to the parental MCF7/LCC1 and MCF-7 cells. Progesterone receptor expression remains estrogen inducible in MCF7/LCC2 cells, although to levels significantly lower than observed in MCF-7 and MCF7/LCC1 cells. MCF7/LCC2 cells form tumors in ovariectomized nude mice without estrogen supplementation, and these tumors are tamoxifen resistant but can be estrogen stimulated. Significantly, MCF7/LCC2 cells have retained sensitivity to the steroidal antiestrogen ICI 182,780. These data suggest that some breast cancer patients who acquire resistance to tamoxifen may not develop cross-resistance to treatment with steroidal antiestrogens.

Footnotes

  • ↵1 This study was supported by Public Health Service Grants 1-R55-CA51782, 5-R01-CA58022 (R. C.), and 5-U01-CA51908 from the National Cancer Institute (R. C., and M. E. L.), the Danish Cancer Society Grants 90-042 and 91-010, and by the Danish Medical Research Council Grant 12-9651-2 (N. B.).

  • ↵2 To whom requests for reprints should be addressed.

  • ↵3 To whom correspondence should be addressed, at Vincent T. Lombardi Cancer Research Center, Georgetown University Medical School, Room S128A, 3800 Reservoir Road N.W., Washington, D.C. 20007.

  • Received March 5, 1993.
  • Accepted June 2, 1993.
  • ©1993 American Association for Cancer Research.
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July 1993
Volume 53, Issue 14
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MCF7/LCC2: A 4-Hydroxytamoxifen Resistant Human Breast Cancer Variant That Retains Sensitivity to the Steroidal Antiestrogen ICI 182,780
Nils Brünner, Thomas L. Frandsen, Claus Holst-Hansen, Mian Bei, Erik W. Thompson, Alan E. Wakeling, Marc E. Lippman and Robert Clarke
Cancer Res July 15 1993 (53) (14) 3229-3232;

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MCF7/LCC2: A 4-Hydroxytamoxifen Resistant Human Breast Cancer Variant That Retains Sensitivity to the Steroidal Antiestrogen ICI 182,780
Nils Brünner, Thomas L. Frandsen, Claus Holst-Hansen, Mian Bei, Erik W. Thompson, Alan E. Wakeling, Marc E. Lippman and Robert Clarke
Cancer Res July 15 1993 (53) (14) 3229-3232;
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