Kelley M K, Engqvist-Goldstein A, Montali J A, Wheatley J B, Schmidt D E, Kauvar L M
Terrapin Technologies, Inc., South San Francisco, CA 94080.
Biochem J. 1994 Dec 15;304 ( Pt 3)(Pt 3):843-8. doi: 10.1042/bj3040843.
The determination of GST levels in blood has been proposed to a marker of tumour burden in general, whereas level of the P1 isoenzyme has been identified as a prognostic factor for breast-cancer patients receiving no adjuvant chemotherapy. Particular glutathione S-transferase (GST) isoenzymes differ in their substrate specificity, however, and their presence or absence might therefore account for the resistance of tumours to particular chemotherapeutic drugs, as already established for cultured cell lines. Determination of the GST isoenzyme profile of a cancer tissue could have prognostic value in the selection of treatment if the levels of expression/activity show a degree of variation comparable with that exhibited by actual patient responses. Using reversed-phase h.p.l.c. to quantify affinity-isolated GSTs, we have analysed full isoenzyme profiles in the first large sample of matched normal and cancer human tissues (18 breast-cancer patients). In no patients did the tumour tissues express any isoenzymes that were not found in normal breast tissue. In addition to the GSTs, another enzyme, identified as enoyl-CoA isomerase, was regularly found in breast tissue cytosol following elution from a hexyl-glutathione affinity column. In most cases, the average level of GST was substantially elevated in the cancer tissues above the levels in normal breast tissue from the same patient. Furthermore, the relative levels of the isoenzymes were substantially more variable in the cancer samples than in the normal breast tissue, providing a plausible mechanism for the well established variable response to treatment.
血液中谷胱甘肽 S-转移酶（GST）水平的测定通常被认为是肿瘤负荷的一个指标，而P1同工酶的水平已被确定为未接受辅助化疗的乳腺癌患者的一个预后因素。然而，特定的谷胱甘肽 S-转移酶（GST）同工酶在底物特异性方面存在差异，因此它们的存在与否可能是肿瘤对特定化疗药物产生耐药性的原因，这在培养的细胞系中已经得到证实。如果癌症组织中GST同工酶的表达/活性水平显示出与实际患者反应相当的变化程度，那么其同工酶谱的测定在治疗选择中可能具有预后价值。我们使用反相高效液相色谱法（h.p.l.c.）对亲和分离的GST进行定量，分析了第一组大量匹配的正常和癌症人体组织样本（18例乳腺癌患者）中的完整同工酶谱。在所有患者中，肿瘤组织均未表达正常乳腺组织中未发现的任何同工酶。除了GST外，从己基谷胱甘肽亲和柱洗脱后，在乳腺组织胞质溶胶中还经常发现另一种酶，被鉴定为烯酰辅酶A异构酶。在大多数情况下，癌症组织中GST的平均水平比同一患者正常乳腺组织中的水平大幅升高。此外，癌症样本中同工酶的相对水平比正常乳腺组织中的变化大得多，这为已确立的治疗反应差异提供了一个合理的机制。
