ESTROGEN-INDUCED CHANGES IN BREAST CANCER CELLS

这项研究的长远目的是开发一种非 利用MRS表征雌激素的侵入性方法 乳腺癌的反应性。 为此，具体 雌激素和抗雌激素调节的代谢活性 将在人类乳腺癌细胞系中表征， 类固醇激素受体：MCF-7、T47 D和ZR-75-1。 这项研究是我们总体努力的一部分， 激素引起的生殖器官变化， 相关恶性肿瘤（见附录）。 搜索将集中在已知的活动， 增强雌激素在真正的靶器官，如：1） 肌酸激酶（BB同工酶）的活性，一种有利的早期 雌激素作用的标志物; 2）雌激素作用的几种关键酶 糖酵解途径;和3）葡萄糖-6-磷酸脱氢酶 （G6 PD），其mRNA的产生增加， 观察 此外，预计监测能力 在活跃的生长细胞中， 发现了无法预测的变化， 磷酸胆碱的甘油衍生物的浓度和 磷酸乙醇胺 核磁共振波谱将是本研究的主要工具。 方法 在核磁共振过程中保持细胞存活、活跃和生长 制定了测量。 31-P NMR将用于 确定细胞的能量学和 磷酸盐转移反应 13-C NMR研究将主要 专注于标记底物的真实的跟踪， 中间体和最终产品提供了通量的测量 通过糖酵解酶和G6 PD。 1-H NMR 测量和1-H观察到的13-C去耦序列将 补充13-C的结果。 方法和结果 这项研究将随后用于MRS研究这些 人乳腺癌细胞系，植入裸鼠， 乳腺肿瘤的研究

The long range purpose of this research is to develop a non invasive method using MRS for the characterization of estrogen responsiveness of breast carcinoma. To that end, specific metabolic activities modulated by estrogens and by antiestrogens will be characterized in human breast cancer cell lines that retain the receptors for steroid hormones: MCF-7, T47D and ZR-75-1. This research is part of our general efforts to characterize hormonal induced changes in the reproductive organs and associated malignancies (see Appendix). The search will concentrate on activities that are known to be enhanced by estrogen in genuine target organs such as: 1) the activity of creatine kinase (the BB isozyme), a favored early marker of estrogen action; 2) several key enzymes of the glycolytic pathway; and 3) glucose-6-phosphate dehydrogenase (G6PD), for which increased production of mRNA has been observed. In addition, it is anticipated that the ability to monitor the metabolism on line, in active growing cells, will lead to the discovery of unpredicted changes as seem to occur with the concentration of the glycerol derivatives of phosphorylcholine and phosphorylethanolamine. NMR spectroscopy will be the main tool in this study. Methods for keeping the cells alive, active and growing during the NMR measurements were developed. 31-P NMR will be employed for determining the energetics of the cells and the kinetics of phosphate transfer reactions. 13-C NMR studies will mainly concentrate on real time follow up of labeled substrates, intermediates, and end products providing a measure of the fluxes through the glycolytic enzymes and G6PD. 1-H NMR measurements and 1-H observed 13-C decoupled sequences will complement the 13-C results. The methodologies and the results of this research will subsequently be used in MRS studies of these human breast cancer cell lines, implanted in nude mice, and of breast tumors in humans.