Sonne-Hansen K, Lykkesfeldt A E
Department of Tumor Endocrinology, Institute of Cancer Biology, Danish Cancer Society, Strandboulevarden 49, DK-2100 Copenhagen, Denmark.
J Steroid Biochem Mol Biol. 2005 Jan;93(1):25-34. doi: 10.1016/j.jsbmb.2004.11.005. Epub 2005 Jan 27.
Estrogens produced within breast tumors may play a pivotal role in growth stimulation of the breast cancer cells. However, it is elusive whether the epithelial breast cancer cells themselves synthesize estrogens, or whether the surrounding tumor stromal cells synthesize and supply the cancer cells with estrogen. The aromatase enzyme catalyzes the estrogen production, aromatizing circulating androgens into estrogens. The aim of this study was to investigate aromatase expression and function in a model system of human breast cancer, using the estrogen responsive human MCF-7 breast cancer cell line. Cells were cultured in a low estrogen milieu and treated with estrogens, aromatizable androgens or non-aromatizable androgens. Cell proliferation, expression of estrogen-regulated proteins and aromatase activity were investigated. The MCF-7 cell line was observed to express sufficient aromatase enzyme activity in order to aromatize the androgen testosterone, resulting in a significant cell growth stimulation. The testosterone-mediated growth effect was completely inhibited by the aromatase inhibitors letrozole and 4-hydroxy-androstenedione. Expression studies of estrogen-regulated proteins confirmed that testosterone was aromatized to estrogen in the MCF-7 cells. Thus, the results indicate that epithelial breast cancer cells possess the ability to aromatize circulating androgens to estrogens.
乳腺肿瘤内产生的雌激素可能在刺激乳腺癌细胞生长中起关键作用。然而，尚不清楚乳腺上皮癌细胞自身是否合成雌激素，或者周围肿瘤基质细胞是否合成并向癌细胞供应雌激素。芳香化酶催化雌激素生成，将循环雄激素转化为雌激素。本研究的目的是使用雌激素反应性人MCF-7乳腺癌细胞系，在人乳腺癌模型系统中研究芳香化酶的表达和功能。细胞在低雌激素环境中培养，并用雌激素、可芳香化雄激素或不可芳香化雄激素处理。研究细胞增殖、雌激素调节蛋白的表达和芳香化酶活性。观察到MCF-7细胞系表达足够的芳香化酶活性，以便将雄激素睾酮芳香化，从而显著刺激细胞生长。芳香化酶抑制剂来曲唑和4-羟基雄烯二酮完全抑制了睾酮介导的生长效应。雌激素调节蛋白的表达研究证实，睾酮在MCF-7细胞中被芳香化为雌激素。因此，结果表明乳腺上皮癌细胞具有将循环雄激素芳香化为雌激素的能力。
