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

T47D-ER beta breast cancer cells with tetracycline-dependent ER beta expression and constant ER alpha expression can be used to investigate effects of varying ER alpha/ER beta ratios on estrogen-induced cellular responses. This study defines conditions at which ER alpha/ER beta ratios in T47D-ER beta cells best mimic ER alpha/ER beta ratios in breast and other estrogen-sensitive tissues in vivo in rat as well as in human. Protein and mRNA levels of ER alpha and ER beta were analyzed in T47D-ER beta cells exposed to a range of tetracycline concentrations and compared to ER alpha and ER beta levels found in breast, prostate, and uterus from rat and human origin. The ER alpha/ER beta ratio in T47D-ER beta cells exposed to >150 ng/ml tetracycline is comparable to the ratio found in rat mammary gland and in human breast tissue. The ER alpha/ER beta ratio of other estrogen-sensitive rat and human tissues can also be mimicked in T47D-ER beta cells. The ER alpha/ER beta 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-ER beta cells as model for estrogen-responsive tissues. Using 17 beta-estradiol and the T47D-ER beta cells under the conditions defined to mimic various tissues it could be demonstrated how these different tissues vary in their proliferative response. (C) 2013 Elsevier Ltd. All rights reserved.