Relation of estrogen receptor expression to clonal growth and antiestrogen effects on human breast cancer cells.

Expression of estrogen receptor (ER) was studied in the ER-positive human breast cancer cell line MCF-7 using immunoperoxidase staining with monoclonal antibodies to ER. Using a soft agar colony assay and liquid culture, effects of growth and the antiestrogen tamoxifen were examined. Heterogeneity in expression of ER was observed between different clones in the agar cultures as well as among cells within the same clone. Clonal expression of ER increased progressively with increasing cell number within a clone. At pharmacological doses, tamoxifen significantly reduced clonal growth but also markedly reduced the expression of ER within clones that grew despite the presence of the antiestrogen. These findings are consistent with the hypothesis that ER-positive colonies arise from ER-negative progenitors and that ER expression occurs along with differentiation of cells within clones. Furthermore, the findings are consistent with tamoxifen exerting its antineoplastic action beyond the level of the tumor stem cell. Such therapy would therefore be capable of suppression but not eradication of breast cancer clonal progenitors.