Influence of Cellular ER /ER  Ratio on the ER -Agonist Induced Proliferation of Human T47D Breast Cancer Cells (original) (raw)

Breast cancer cells show overexpression of estrogen receptor (ER) a relative to ERb compared to normal breast tissues. This observation has lead to the hypothesis that ERb may modulate the proliferative effect of ERa. This study investigated how variable cellular expression ratios of the ERa and ERb modulate the effects on cell proliferation induced by ERa or ERb agonists, respectively. Using human osteosarcoma (U2OS) ERa or ERb reporter cells, propyl-pyrazole-triol (PPT) was shown to be a selective ERa and diarylpropionitrile (DPN) a preferential ERb modulator. The effects of these selective estrogen receptor modulators (SERMs) and of the model compound E2 on the proliferation of T47D human breast cancer cells with tetracyclinedependent expression of ERb (T47D-ERb) were characterized. E2-induced cell proliferation of cells in which ERb expression was inhibited was similar to that of the T47D wild-type cells, whereas this E2-induced cell proliferation was no longer observed when ERb expression in the T47D-ERb cells was increased. In the T47D-ERb cell line, DPN also appeared to be able to suppress cell proliferation when levels of ERb expression were high. In the T47D-ERb cell line, PPT was unable to suppress cell proliferation at all ratios of ERa/ERb expression, reflecting its ability to activate only ERa and not ERb. It is concluded that effects of estrogen-like compounds on cell proliferation are dependent on the actual ERa/ERb expression levels in these cells or tissues and the potential of the estrogen agonists to activate ERa and/or ERb.