Gene expression of ABC proteins in hepatocellular carcinoma, perineoplastic tissue, and liver diseases
Gene expression of ABC proteins in hepatocellular carcinoma, perineoplastic tissue, and liver diseases
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DOI：
10.1007/bf03402158
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发表时间：
2002-06-01
影响因子：
5.7
通讯作者：
Tiribelli, C
中科院分区：
文献类型：
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作者：
Bonin, S;Pascolo, L;Tiribelli, C
背景：肝细胞癌（HCC）的发展是肝硬化自然病程中的常见事件。然而，有效的治疗受到与属于 ABC 家族转运蛋白的多药耐药 (MDR) 蛋白表达相关的耐药性的阻碍。研究编码这些蛋白的基因表达可能有助于解释 HCC 对化疗的潜在敏感性。 材料和方法：通过定量 RT-PCR 分析，在取自 9 例 HCC、16 例肝硬化、10 例慢性肝外胆汁淤积症和 10 例慢性肝外胆汁淤积症的石蜡包埋组织中研究 MRP1、MRP2、MRP3、MDR1 和 MDR3 的表达。 正常肝脏16例。在 HCC 病例中，在显微镜辅助显微解剖后评估肿瘤组织和肿瘤周围组织中的基因表达。结果：MRP1 在 HCC 和肿瘤周围组织中显着且类似地过表达。 MRP2和MDR1在HCC中也升高，但表达水平与癌旁组织的表达水平不相关。在肝硬化肝和慢性胆汁淤积期间表达水平降低或正常。 MDR3 的表达在所有研究条件下均未变化。结论：多药耐药蛋白（特别是 MRP1、MRP2 和 MDR1）的基因表达在 HCC 期间增加。就 MRP1 而言，肿瘤组织和肿瘤周围组织中的表达程度相似，但 MRP2 和 MDR1 的情况并非如此。 ABC蛋白表达模式的评估可能为HCC的诊断和治疗提供重要信息。
Background: The development of hepatocellular carcinoma (HCC) is a frequent event during the natural history of cirrhosis. Effective treatment is, however, hampered by drug resistance related to the expression of multidrug resistance (MDR) proteins belonging to the ABC family transporters. Studying expression of genes coding for these proteins may help to explain the potential sensitivity of HCC to chemotherapy.Material and Methods: The expression of MRP1, MRP2, MRP3, MDR1, and MDR3 was investigated by quantitative RT-PCR analyses in paraffin-embedded tissues obtained from 9 cases of HCC, 16 cases of cirrhosis, 10 cases of chronic extrahepatic cholestasis, and 16 cases of normal liver. In HCC cases, gene expression was assessed both in neoplastic and perineoplastic tissue after microscopically assisted microdissection.Results: MRP1 was significantly and similarly overexpressed in HCC and perineoplastic tissue. MRP2 and MDR1 were also increased in HCC, but the level of expression did not correlate with that of perineoplastic tissue. The level of expression was either reduced or normal in cirrhotic liver and during chronic cholestasis. Expression of MDR3 was unchanged in all conditions investigated.Conclusions: The genetic expression of multi-drug resistance proteins, in particular MRP1, MRP2, and MDR1, is increased during HCC. In the case of MRP1, the extent of expression is similar in neoplastic and perineoplastic tissue, but this is not the case for MRP2 and MDR1. The assessment of ABC protein expression pattern may provide important information for the diagnosis and treatment of HCC.