Division of Toxicology, Wageningen University, Tuinlaan 5, 6703 HE Wageningen, The Netherlands.
Toxicol In Vitro. 2013 Sep;27(6):1753-61. doi: 10.1016/j.tiv.2013.04.014. Epub 2013 May 13.
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.
具有四环素依赖性 ERβ 表达和恒定 ERα 表达的 T47D-ERβ 乳腺癌细胞可用于研究 ERα/ERβ 比值变化对雌激素诱导的细胞反应的影响。本研究确定了 T47D-ERβ 细胞中 ERα/ERβ 比值在大鼠体内以及在人类体内模拟乳腺和其他雌激素敏感组织中 ERα/ERβ 比值的条件。分析了暴露于不同四环素浓度的 T47D-ERβ 细胞中 ERα 和 ERβ 的蛋白和 mRNA 水平，并与来自大鼠和人类的乳腺、前列腺和子宫中发现的 ERα 和 ERβ 水平进行了比较。暴露于 >150ng/ml 四环素的 T47D-ERβ 细胞中的 ERα/ERβ 比值与大鼠乳腺和人乳腺组织中发现的比值相当。其他雌激素敏感的大鼠和人类组织中的 ERα/ERβ 比值也可以在 T47D-ERβ 细胞中模拟。MCF-7 和天然 T47D 乳腺癌细胞系中的 ERα/ERβ 比值不能反映分析的大鼠和人类组织中的比值，这进一步支持了使用 T47D-ERβ 细胞作为雌激素反应性组织的模型。使用 17β-雌二醇和在模拟各种组织的条件下的 T47D-ERβ 细胞，证明了这些不同组织在增殖反应方面的差异。
