Department of Medical Genetics, Tehran University of Medical Sciences, Tehran, Iran.
Med Oncol. 2010 Jun;27(2):474-80. doi: 10.1007/s12032-009-9237-5. Epub 2009 May 27.
Tamoxifen is the most common antiestrogen used in the treatment of estrogen-positive breast cancer but its adverse effects and also resistance to this drug are serious challenges in the treatment of breast cancer. Characterization of mechanisms responsible for these adverse effects can lead to design of more efficient therapeutic strategies for the treatment of breast cancer. Here, we used a cellular model to evaluate the effects of autocrine expression of human growth hormone on responses of cells to tamoxifen. Our results imply for the first time that autocrine expression of growth hormone in human breast adenocarcinoma cell line, MCF-7, results in increase in cell proliferative capacity of cells even in the presence of tamoxifen. This effect may be due to up-regulation of G-coupled estrogen receptor, GPR30, which is activated by tamoxifen.
他莫昔芬是治疗雌激素阳性乳腺癌最常用的抗雌激素药物,但它的不良反应和对这种药物的耐药性是乳腺癌治疗中的严重挑战。对这些不良反应机制的描述可以为治疗乳腺癌设计更有效的治疗策略。在这里,我们使用细胞模型来评估自分泌表达人生长激素对细胞对他莫昔芬反应的影响。我们的结果首次表明,在人乳腺癌腺癌细胞系 MCF-7 中自分泌表达生长激素会导致细胞增殖能力增加,即使存在他莫昔芬也是如此。这种作用可能是由于他莫昔芬激活的 G 蛋白偶联雌激素受体 GPR30 的上调所致。