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MCF7/LCC2: A 4-Hydroxytamoxifen Resistant Human Breast Cancer Variant That Retains Sensitivity to the Steroidal Antiestrogen ICI 182,780¹

Vincent T. Lombardi Cancer Center [N. B., M. B., E. W. T., T. L. F., M. E. L., R. C.] and Departments of Physiology and Biophysics [R. C.] and Anatomy and Cell Biology [E. W. T.], Georgetown University Medical School, Washington, D.C. 20007; The Finsen Institute, 49 Strandboulevarden, 2100 Copenhagen, Denmark [N. B., T. L. F., C. H-H.]; and Cancer Research Department, ZENECA Pharmaceuticals, Alderley Park, Macclesfield, Cheshire, United Kingdom [A. W.]

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.

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 3/ 5/93. Accepted 6/ 2/93.

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