Mohamadi Azam, Aghaei Mahmoud, Panjehpour Mojtaba
Department of Biochemistry and Bioinformatics Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, I.R. Iran.
Res Pharm Sci. 2018 Feb;13(1):57-64. doi: 10.4103/1735-5362.220968.
Estrogen is a steroid hormone that plays a key role in the development and regulation of reproductive system. It has been shown that estrogen is related to breast cancer development through binding to its receptors. In order to uncover the estrogen effects on adenosine receptor expression, estrogen-positive MCF-7 cells were used to treat with agonist and antagonist of estrogen and then the mRNA expression of adenosine receptor subtypes were evaluated. Estrogen-positive MCF-7 cells were treated with various concentrations of 17β estradiol (E2) as an estrogen agonist, and ICI 182,780 as an estrogen antagonist. The gene expression of adenosine receptor subtypes were detected by real time RT-PCR. The results of MTT assay showed that E2 increased cell viability in a dose dependent manner. The expression pattern of all adenosine receptor subtypes are as follow; A2b > A1 > A2a > A3 in untreated MCF-7 cells. Obtained results showed that E2 incubation at 0.001-0.01 μM led to up-regulation of A1ARs, A2aARs and A3ARs dose dependently. E2 at 0.001 μM also had no significant effect on A2bARs expression but, at higher doses induced a considerable decrease in mRNA A2bARs expression. Treatment with antagonist confirmed that up-regulation of these receptors is mediated by estrogen receptor. Taken together, our results indicate that treatment of MCF-7 cells with E2 led to up-regulation of adenosine receptors. However, these effects were partially restored by treatment with antagonist suggesting that such effects are mediated by estrogen receptors.
雌激素是一种类固醇激素，在生殖系统的发育和调节中起关键作用。研究表明，雌激素通过与受体结合与乳腺癌的发生发展相关。为了揭示雌激素对腺苷受体表达的影响，使用雌激素阳性的MCF-7细胞用雌激素激动剂和拮抗剂进行处理，然后评估腺苷受体亚型的mRNA表达。用不同浓度的17β雌二醇（E2）作为雌激素激动剂，以及ICI 182,780作为雌激素拮抗剂处理雌激素阳性的MCF-7细胞。通过实时RT-PCR检测腺苷受体亚型的基因表达。MTT分析结果表明，E2以剂量依赖性方式增加细胞活力。在未处理的MCF-7细胞中，所有腺苷受体亚型的表达模式如下：A2b > A1 > A2a > A3。获得的结果表明，在0.001-0.01μM浓度下孵育E2导致A1AR、A2aAR和A3AR剂量依赖性上调。0.001μM的E2对A2bAR的表达也没有显著影响，但在较高剂量下会导致mRNA A2bAR表达显著下降。用拮抗剂处理证实这些受体的上调是由雌激素受体介导的。综上所述，我们的结果表明，用E2处理MCF-7细胞会导致腺苷受体上调。然而，用拮抗剂处理可部分恢复这些作用，表明这种作用是由雌激素受体介导的。
