肾细胞癌中耐药因子（P-糖蛋白、谷胱甘肽S-转移酶-pi和拓扑异构酶II）的表达及其与原癌基因产物的相互关系。

Expression of resistance factors (P-glycoprotein, glutathione S-transferase-pi, and topoisomerase II) and their interrelationship to proto-oncogene products in renal cell carcinomas.

作者信息

Volm M, Kästel M, Mattern J, Efferth T

机构信息

German Cancer Research Center, Heidelberg.

出版信息

Cancer. 1993 Jun 15;71(12):3981-7. doi: 10.1002/1097-0142(19930615)71:12<3981::aid-cncr2820711231>3.0.co;2-a.

DOI:10.1002/1097-0142(19930615)71:12<3981::aid-cncr2820711231>3.0.co;2-a

PMID:8099529

Abstract

BACKGROUND

This study investigates whether or not an interrelationship exists between the expression of resistance-related proteins (P-glycoprotein, glutathione S-transferase, topoisomerase II) and proto-oncogene products (c-fos, c-myc, c-K-ras, epidermal growth factor receptor [EGF-R], and c-neu proteins.)

METHODS

Thirty-eight human renal cell carcinomas of previously untreated patients were analyzed for expression of P-glycoprotein (P-170), glutathione S-transferase-pi (GST-pi), topoisomerase II (Topo II) and proto-oncogene proteins by means of immunohistochemistry. Because of significant heterogeneity in most tumor biopsies, all analyses were done on tumor-derived primary cell culture lines on the third or fourth passage.

RESULTS

An interrelationship between increased expression of P-170 and GST-pi and down-regulation of Topo II was found. Expression of the c-fos protein was seen in 66% of the tumors; expression of the c-myc protein, in 50%; of the c-K-ras protein, in 16%; of the EGF-R protein, in 61%; and of the c-neu protein, in 54% of the tumors. A significant correlation between the resistance factors and the c-fos, EGF-R, and c neu-proteins was observed (GST/c-fos, P = 0.012; Topo II/c-fos, P = 0.024; P-170/EGF-R, P < 0.001; GST/EGF-R, P = 0.018; Topo II/EGF-R, P = 0.027; P-170/c-neu, P = 0.005; GST/c-neu, P = 0.018; Topo II/EGF-R, P = 0.027; P-170/c-neu, P = 0.005; GST/c-neu, P = 0.008; Topo II/c-neu, P = 0.05). In contrast, interrelationships between resistance proteins and c-myc and c-K-ras proteins were not found. A significant interrelationship between the investigated resistance-related proteins or proto-oncogene proteins and the stage or grading of the tumors was not observed.

CONCLUSIONS

The results demonstrate that in renal cell carcinomas a significant relationship exists between resistance-related proteins, such as P-170, GST-pi, or Topo II, and proto-oncogenes, such as c-fos, c-erbB1, and c-neu.

摘要

背景

本研究调查耐药相关蛋白（P-糖蛋白、谷胱甘肽S-转移酶、拓扑异构酶II）与原癌基因产物（c-fos、c-myc、c-K-ras、表皮生长因子受体[EGF-R]和c-neu蛋白）之间是否存在相互关系。

方法

采用免疫组织化学方法分析38例未经治疗的患者的人肾细胞癌中P-糖蛋白（P-170）、谷胱甘肽S-转移酶-pi（GST-pi）、拓扑异构酶II（Topo II）和原癌基因蛋白的表达。由于大多数肿瘤活检存在显著异质性，所有分析均在传代3次或4次的肿瘤来源的原代细胞系上进行。

结果

发现P-170和GST-pi表达增加与Topo II下调之间存在相互关系。66%的肿瘤中可见c-fos蛋白表达；50%的肿瘤中可见c-myc蛋白表达；16%的肿瘤中可见c-K-ras蛋白表达；61%的肿瘤中可见EGF-R蛋白表达；54%的肿瘤中可见c-neu蛋白表达。观察到耐药因子与c-fos、EGF-R和c-neu蛋白之间存在显著相关性（GST/c-fos，P = 0.012；Topo II/c-fos，P = 0.024；P-170/EGF-R，P < 0.001；GST/EGF-R，P = 0.018；Topo II/EGF-R，P = 0.027；P-170/c-neu，P = 0.005；GST/c-neu，P = 0.018；Topo II/EGF-R，P = 0.027；P-170/c-neu，P = 0.005；GST/c-neu，P = 0.008；Topo II/c-neu，P = 0.05）。相反，未发现耐药蛋白与c-myc和c-K-ras蛋白之间存在相互关系。未观察到所研究的耐药相关蛋白或原癌基因蛋白与肿瘤分期或分级之间存在显著相互关系。