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

N M Evers, T M C van de Klundert, Y M van Aesch, S Wang, W K de Roos, A Romano, L H J de Haan, A J Murk, A G H Ederveen, I M C M Rietjens, J P Groten
Toxicology in Vitro: An International Journal Published in Association with BIBRA 2013, 27 (6): 1753-61
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.

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