Differential effects of estrogen and antiestrogen on in vitro clonogenic growth of human breast cancers in soft agar.
Of 534 human primary breast cancers provided for clonogenic assay in vitro, 276 (51.7%) developed distinctive colony formation by the soft-agar method. Estrogen receptors (ERs) were assayed by dextran-coated charcoal methods. A total of 65 (23.7%) of 274 breast cancers responded to added 10 nM 17 beta-estradiol (E2) by an increase in the number of colonies per dish of 150% or more of that in the controls treated with dextran-coated charcoal. The ER-positive and ER-negative tumors differed significantly in their response to E2: 55 (29.9%) of 184 ER-positive tumors responded versus 10 (11.1%) of 90 ER-negative tumors. The cancers in which the number of colonies increased to 150% or more of that of the controls were considered to be estrogen dependent; those in which the number of colonies increased to less than 150% of the control values were considered to be estrogen independent. When 1 microM tamoxifen (TMX) was added to the medium, 48 (21.3%) of 225 cancers showed a decreased in the number of colonies to 50% or less of that of the controls. Thus, we could separate breast cancers that were TMX sensitive (No. of colonies less than or equal to 50% of that of controls) from those that were TMX resistant (No. of colonies greater than 50% of that of controls). The response to TMX of the ER-positive cancers was significantly higher than that of the ER-negative tumors: 39 (25.5%) of 153 ER-positive tumors responded versus nine (12.5%) of 72 ER-negative tumors. In 153 ER-positive and 71 ER-negative tumors, we evaluated the correlation between the response to E2 and the response to TMX. ER-positive and ER-negative tumors differed significantly in their sensitivities to the two drugs. The TMX sensitivity did not completely correlate with the E2 dependence.(ABSTRACT TRUNCATED AT 250 WORDS)
Nomura
Y
Y
Department of Breast Surgery, National Kyushu Cancer Center Hospital, Fukuoka, Japan.
Tashiro
H
H
Hisamatsu
K
K
D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology*; D004967:Estrogens; D005260:Female; D006801:Humans; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000473:pathology; D013268:Stimulation, Chemical; D013629:Tamoxifen / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
D004967:Estrogens; D013629:Tamoxifen; D004958:Estradiol