EXPRESSION OF GLUTATHIONE S-TRANSFERASES IN NORMAL GASTRIC-MUCOSA AND IN GASTRIC TUMORS

EXPRESSION OF GLUTATHIONE S-TRANSFERASES IN NORMAL GASTRIC-MUCOSA AND IN GASTRIC TUMORS
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DOI:
10.1093/carcin/11.9.1593
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发表时间:
1990-09-01
期刊:
影响因子:
4.7
通讯作者:
THIES, E
THIES, E
中科院分区:
医学2区
文献类型:
--
作者:
PETERS, WHM;WORMSKAMP, NGM;THIES, E

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研究人员对来自 10 名不同患者的正常胃粘膜及其相匹配的胃肿瘤的谷胱甘肽 S-转移酶进行了研究。纯化转移酶并随后研究同工酶组成。谷胱甘肽 S-转移酶 (GST)-.pi。大量存在于所有样本中。 .alpha 类。 GST 存在于 10 个正常样本中的 9 个和 6 个肿瘤中。在恶性组织中,表达GST-.pi。以牺牲 .alpha 类为代价而增加。商品及服务税。在 6 名患者中,GST-.pi./GST-.alpha 的比率。肿瘤组织中的含量高于正常组织。使用单克隆抗体 GST-.mu 进行蛋白质印迹。结果显示,四名患者的正常组织和恶性组织中都存在这种酶,其他六名患者的胃组织中完全没有发现这种酶。如果存在,GST-.mu。仅占总 GST 蛋白质的百分之几。 GST-.pi。通过用针对 GST-.pi 的单克隆抗体处理的蛋白质印迹的光密度分析来定量。总 GST 酶活性以及 GST-.pi 的绝对量。与匹配的正常粘膜相比,肿瘤中的蛋白质显着更高。 GST-.pi 过度表达的重要性。以前是未知的。然而,这种现象在许多难治性肿瘤中频繁发生,并且正如现在在胃癌中所显示的那样,表明 GST-.pi 的作用。在抗癌耐药机制中。
Glutathione S-transferases from both normal gastric mucosa and its matched gastric tumors from 10 different patients were investigated. The transferases were purified and subsequently the isoenzyme composition was studied. Glutathione S-transferase (GST)-.pi. was present in all specimens in large amounts. Class .alpha. GSTs were present in 9 out of 10 normal specimens and in six tumors. In malignant tissue, expression of GST-.pi. was increased at the expense of class .alpha. GST. In six patients, the ratio GST-.pi./GST-.alpha. was higher in tumorous versus normal tissue. On a Western blot, using a monoclonal antibody, GST-.mu. was shown to be present in both normal and malignant tissue from four patients, the other six patients completely missed the enzyme in their gastric tissue. When present, GST-.mu. amounts to only a few per cent of total GST protein. GST-.pi. was quantified by densitometric analysis of Western blots, treated with a monoclonal antibody against GST-.pi.. Both total GST enzyme activity as well as the absolute amounts of GST-.pi. protein were significantly higher in the tumors, as compared to its matched normal mucosa. The impotance of this overexpression of GST-.pi. was previously unknown. However, the frequent occurrence of this phenomenon in many refractory tumors, and as shown now also in gastric cancers, suggests a role for GST-.pi. in the mechanism of anti-cancer drug resistance.