研究动态
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Selenium依赖的谷胱甘肽过氧化物酶表达与人类乳腺癌细胞的雌激素受体含量呈反比关系。

Selenium-dependent glutathione peroxidase expression is inversely related to estrogen receptor content of human breast cancer cells.

发表日期:1991 Aug
作者: A J Townsend, C S Morrow, B K Sinha, K H Cowan
来源: Cancer Communications

摘要:

缺乏雌激素受体(ER)的人类乳腺肿瘤与ER阳性乳腺癌患者相比预后更为不良。我们实验室以前的研究表明,对阿霉素耐药(ADR)选择的多药耐药人类乳腺癌细胞系表现出明显增加的 pi 类谷胱甘肽 S-转移酶(GST-pi)和依赖硒的谷胱甘肽过氧化物酶的表达。这些研究还揭示了 ER 状态与六种人类乳腺癌细胞系和原发肿瘤样本中 GST-pi 表达的反向关系。在本研究中,我们研究了 ER 状态和这些细胞的几个生物学特性之间的关系,包括它们的谷胱甘肽过氧化物酶(GSH-Px)和过氧化氢酶表达水平、通过 ADR 氧化还原循环生成有毒羟自由基(degrees OH)的能力以及对ADR和氧化剂 H2O2细胞毒作用的敏感性。我们的研究结果显示,在这些细胞系中,GSH-Px的表达与ER状态呈反向关系,而过氧化氢酶并无此关系。通过 ADR 处理的细胞所诱导的 degrees OH 的形成与这些细胞中的 GSH-Px 活性成反比例关系,因此与 ER 状态直接相关。然而,这些细胞对 ADR 或 H2O2 的敏感性并不一致地与 ER 状态、GSH-Px 或过氧化氢酶活性有关,也不与 ADR 诱导的 degrees OH 自由基的形成有关。这些结果表明,在所研究的条件下,这些参数不能预测这些细胞系对氧化损伤的易感性。
The absence of estrogen receptors (ER) in human breast tumors has been associated with a poorer prognosis compared to patients with ER positive breast cancer. Previous studies from our laboratory have shown that a multidrug resistant human breast cancer cell line selected for resistance to Adriamycin (ADR) exhibited markedly increased expression of both the pi class glutathione S-transferase (GST-pi) and the selenium-dependent glutathione peroxidase. These studies also revealed that the ER status was inversely related to the expression of GST-pi in six human breast cancer cell lines and primary tumor specimens. In the present study, we have examined the relationship between ER status and several biological properties of these cells, including their levels of glutathione peroxidase (GSH-Px) and catalase expression, their capacity to generate toxic hydroxyl radicals (degrees OH) by redox cycling of ADR, and their sensitivities to the cytotoxic effects of ADR and the oxidant, H2O2. Our results show that expression of GSH-Px, but not catalase, is inversely related to the ER status in these cell lines. Formation of the degree OH induced by treatment of cells with ADR was inversely proportional to the GSH-Px activity in these cell lines, and thus directly related to the ER status. Sensitivity of these cells to ADR or to H2O2, however, was not consistently related to ER status, GSH-Px, or catalase activity, or to ADR induced degree OH radical formation. These results indicate that these parameters are not predictive of cellular susceptibility to oxidative damage in these cell lines under the conditions studied.