Human T47D-ERβ breast cancer cells with tetracycline-dependent ERβ expression reflect ERα/ERβ ratios in rat and human breast tissue

•ERα/ERβ ratios are defined in T47D-ERβ cells with tetracycline dependent ERβ.•ERα/ERβ ratios of T47D-ERβ cells can mimic ratios in breast, prostate and uterus.•Conditions at which the T47D-ERb cells best mimic in vivo tissues are established.•Estradiol induced cell proliferation varies with the ERα/ERβ ratio.•ERβ levels in MCF-7 and native T47D cell lines do not reflect levels in tissues. T47D-ERβ breast cancer cells with tetracycline-dependent ERβ expression and constant ERα expression can be used to investigate effects of varying ERα/ERβ ratios on estrogen-induced cellular responses. This study defines conditions at which ERα/ERβ ratios in T47D-ERβ cells best mimic ERα/ERβ ratios in breast and other estrogen-sensitive tissues in vivo in rat as well as in human. Protein and mRNA levels of ERα and ERβ were analyzed in T47D-ERβ cells exposed to a range of tetracycline concentrations and compared to ERα and ERβ levels found in breast, prostate, and uterus from rat and human origin. The ERα/ERβ ratio in T47D-ERβ cells exposed to >150ng/ml tetracycline is comparable to the ratio found in rat mammary gland and in human breast tissue. The ERα/ERβ ratio of other estrogen-sensitive rat and human tissues can also be mimicked in T47D-ERβ cells. The ERα/ERβ ratio found in MCF-7 and native T47D breast cancer cell lines did not reflect ratios in analyzed rat and human tissues, which further supports the use of T47D-ERβ cells as model for estrogen-responsive tissues. Using 17β-estradiol and the T47D-ERβ cells under the conditions defined to mimic various tissues it could be demonstrated how these different tissues vary in their proliferative response.