Evans T R, Chander S K, Rowlands M G, Coombes R C
CRC Department of Medicine Oncology, Charing Cross Hospital, UK.
Br J Cancer. 1992 Jan;65(1):72-6. doi: 10.1038/bjc.1992.13.
Oestrone sulphatase may be an important means of production of intra-tumoural oestrogens in breast cancer cells. The N-nitrosomethylurea induced rat mammary tumours, which is a good model of human breast carcinoma, was utilised to examine the significance of intra-tumoural oestrone sulphatase levels. The particular fraction (100,000 g pellet) was prepared from both the liver and the tumour of NMU treated rats and assayed for sulphatase activity. The tumour enzyme had an optimum pH of 7.2, Km value of 14.8 microM and Vmax of 0.90 nmoles min-1 mg-1, while the hepatic enzyme was optimal at pH 7.4, Km of 10.8 microM and Vmax of 3.71 nmoles min-1 mg-1. The relationship of intra-tumoural sulphatase levels with tumour regression and progression in endocrine responsive tumours was investigated. Tumour regression as a result of oophorectomy was associated with a significantly decreased intra-tumoural sulphatase level (mean level = 0.165 nmoles min-1 mg-1) in comparison to a control group (mean level = 0.319 nmoles min-1 mg-1, P less than 0.05) in which the tumours remained stable. This significant difference was not observed in the corresponding hepatic samples suggesting that it is the intra-tumoural rather than the peripheral production of oestrogens by oestrone sulphatase that is important in supporting growth of endocrine responsive tumours.
硫酸雌酮酶可能是乳腺癌细胞中肿瘤内雌激素产生的重要途径。N-亚硝基甲基脲诱导的大鼠乳腺肿瘤是人类乳腺癌的良好模型,用于研究肿瘤内硫酸雌酮酶水平的意义。从NMU处理大鼠的肝脏和肿瘤中制备特定部分(100,000g沉淀),并测定硫酸酯酶活性。肿瘤酶的最适pH为7.2,Km值为14.8 microM,Vmax为0.90纳摩尔·分钟-1·毫克-1,而肝酶在pH 7.4时最适宜,Km为10.8 microM,Vmax为3.71纳摩尔·分钟-1·毫克-1。研究了肿瘤内硫酸酯酶水平与内分泌反应性肿瘤的肿瘤消退和进展之间的关系。与肿瘤保持稳定的对照组(平均水平 = 0.319纳摩尔·分钟-1·毫克-1,P小于0.05)相比,卵巢切除导致的肿瘤消退与肿瘤内硫酸酯酶水平显著降低(平均水平 = 0.165纳摩尔·分钟-1·毫克-1)相关。在相应的肝脏样本中未观察到这种显著差异,这表明硫酸雌酮酶在肿瘤内而非外周产生雌激素对支持内分泌反应性肿瘤的生长很重要。