Influence of cellular ERalpha/ERbeta ratio on the ERalpha-agonist induced proliferation of human T47D breast cancer cells.
Influence of cellular ERalpha/ERbeta ratio on the ERalpha-agonist induced proliferation of human T47D breast cancer cells.
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DOI：
10.1093/toxsci/kfn141
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发表时间：
2008-10
期刊：
影响因子：
--
通讯作者：
Murk AJ
中科院分区：
文献类型：
--
作者：
Sotoca AM;van den Berg H;Vervoort J;van der Saag P;Ström A;Gustafsson JA;Rietjens I;Murk AJ
与正常乳腺组织相比，乳腺癌细胞显示雌激素受体(ER) α相对于ERβ过表达。这一观察结果导致了ERβ可能调节ERα的增殖作用的假设。本研究分别探讨了ERα和ERβ在不同细胞表达比例下对ERα和ERβ激动剂诱导的细胞增殖的影响。在人骨肉瘤（U2OS） ERα或ERβ报告细胞中，丙基吡唑三醇（PPT）是选择性ERα，二烷基丙腈（DPN）是选择性ERβ调节剂。研究了这些选择性雌激素受体调节剂（SERMs）和模型化合物E2对四环素依赖表达ERβ (T47D-ERβ)的T47D人乳腺癌细胞增殖的影响。e2诱导的ERβ表达被抑制的细胞增殖与T47D野生型细胞相似，而当ERβ表达在T47D-ERβ细胞中增加时，不再观察到e2诱导的细胞增殖。在T47D-ERβ细胞系中，当ERβ表达水平高时，DPN似乎也能够抑制细胞增殖。在T47D-ERβ细胞系中，无论ERα/ERβ的表达比例如何，PPT都无法抑制细胞增殖，这反映了PPT仅激活ERα而不激活ERβ的能力。由此可见，雌激素样化合物对细胞增殖的影响取决于这些细胞或组织中ERα/ERβ的实际表达水平以及雌激素激动剂激活ERα和/或ERβ的潜力。
Breast cancer cells show overexpression of estrogen receptor (ER) α relative to ERβ compared to normal breast tissues. This observation has lead to the hypothesis that ERβ may modulate the proliferative effect of ERα. This study investigated how variable cellular expression ratios of the ERα and ERβ modulate the effects on cell proliferation induced by ERα or ERβ agonists, respectively. Using human osteosarcoma (U2OS) ERα or ERβ reporter cells, propyl-pyrazole-triol (PPT) was shown to be a selective ERα and diarylpropionitrile (DPN) a preferential ERβ 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 tetracycline-dependent expression of ERβ (T47D-ERβ) were characterized. E2-induced cell proliferation of cells in which ERβ expression was inhibited was similar to that of the T47D wild-type cells, whereas this E2-induced cell proliferation was no longer observed when ERβ expression in the T47D-ERβ cells was increased. In the T47D-ERβ cell line, DPN also appeared to be able to suppress cell proliferation when levels of ERβ expression were high. In the T47D-ERβ cell line, PPT was unable to suppress cell proliferation at all ratios of ERα/ERβ expression, reflecting its ability to activate only ERα and not ERβ. It is concluded that effects of estrogen-like compounds on cell proliferation are dependent on the actual ERα/ERβ expression levels in these cells or tissues and the potential of the estrogen agonists to activate ERα and/or ERβ.
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