Kristensen C A, Kristjansen P E, Brünner N, Clarke R, Spang-Thomsen M, Quistorff B
Finsen Center, National University Hospital, Copenhagen, Denmark.
Cancer Res. 1995 Apr 15;55(8):1664-9.
The effect of estrogen withdrawal on energy metabolism was studied in four human breast cancer xenografts: the estrogen-dependent MCF-7 and ZR75-1 and the estrogen-independent ZR75/LCC-3 and MDA-MB-231. The tumors were grown in ovariectomized nude mice with a s.c. implanted estrogen pellet. After Gompertzian growth was verified, the estrogen pellet was removed from half of the animals. In vivo 31P magnetic resonance spectroscopy of the tumors was performed 1 day before and on days 2, 6, and 14 after estrogen removal. Estrogen withdrawal induced a significant increase in the nucleoside triphosphate:Pi ratio in the two estrogen-dependent xenografts, whereas this ratio remained unchanged in the estrogen-independent tumors. In ZR75/LCC-3 tumors a slight decrease in nucleoside triphosphate:Pi was observed following onset of estrogen stimulation after initial growth without estrogen. Extracts of freeze-clamped tumors prepared 14 days after estrogen removal were analyzed for ATP and phosphocreatine content. Our findings suggest a correlation between estrogen withdrawal and the steady-state concentrations of ATP, phosphocreatine, and Pi in human breast cancer xenografts. Discrimination analysis of the pretherapeutic spectra enabled us to identify the tumor line and the estrogen dependence of the tumors in 80-90% of all cases.
雌激素依赖的MCF-7和ZR75-1以及雌激素非依赖的ZR75/LCC-3和MDA-MB-231。将肿瘤接种于皮下植入雌激素丸粒的去卵巢裸鼠体内。在证实肿瘤呈Gompertzian生长后，从半数动物体内取出雌激素丸粒。在雌激素撤除前1天以及撤除后第2、6和14天对肿瘤进行体内31P磁共振波谱分析。雌激素撤除导致两种雌激素依赖的异种移植瘤中核苷三磷酸与无机磷酸（Pi）的比值显著升高，而在雌激素非依赖的肿瘤中该比值保持不变。在ZR75/LCC-3肿瘤中，最初在无雌激素情况下生长，开始给予雌激素刺激后，观察到核苷三磷酸与Pi的比值略有下降。对雌激素撤除14天后制备的冷冻钳夹肿瘤提取物进行ATP和磷酸肌酸含量分析。我们的研究结果表明，雌激素撤除与人乳腺癌异种移植瘤中ATP、磷酸肌酸和Pi的稳态浓度之间存在相关性。治疗前波谱的判别分析使我们能够在80%至90%的所有病例中识别肿瘤细胞系以及肿瘤的雌激素依赖性。
