γ-谷氨酰半胱氨酸合成酶和多药耐药相关蛋白基因在膀胱癌中的表达及相关性分析

Expression and Correlation Analysis of γ-glutamylcysteine Synthetase and Multidurg Resistance-associated Protein Genes in Bladder Cancers

为探讨 γ-谷氨酰半胱氨酸合成酶 (γ- GCS)及多药耐药相关蛋白 (MRPs)与膀胱癌化疗耐药的关系 ,应用逆转录多聚酶链式反应 (Rt- PCR)技术检测了 32例膀胱癌及其癌周正常膀胱粘膜上 γ- GCS亚单位 γ- GCSh、γ- GCSl以及 MRPs家族成员 MRP1 和 MRP2 的 m RNA的表达 ,并以 β- actin m RNA为内对照半定量进行相关分析。结果显示 :γ-GCSh、γ- GCSl、MRP1 和 MRP2 m RNA在癌组织的平均相对表达水平均高于其在正常粘膜的表达 ;γ- GCSh和 MRP1 在化疗复发病例的癌组织的平均表达水平明显高于在未接受过任何化疗的初发病例 ,同时显示两者在癌组织的表达具有较强的相关性 (r=0 .786 ,P<0 .0 1)。提示 :正常细胞的恶性化可上调 γ- GCS和 MRPs的表达 ;膀胱癌临床化疗耐药的形成与 γ- GCSh和 MRP1 的过表达密切相关 。

To investigate in vivo the relationship between γ glutamylcysteine synthetase (γ GCS) and multidrug associated proteins (MRPs) and chemotherapy resistance in bladder cancers, expression of four genes, including both subunits (heavy and light subnits, γ GCSh and γ GCSl) of γ GCS and two members of MRP family, in 64 fresh samples (32 bladder carcinomas and their corresponding normal bladder mucosa) was detected using the reverse transcription polymerase chain reaction (Rt PCR) methods with β action mRNA as an internal control. The results showed that the mean expression levels of γ GCSh, γ GCSl, MRP 1 and MRP 2 in carcinoma tissues were significantly higher than those of their corresponding normal bladder mucosa; The expression levels of γ GCSh and MRP 1 in the recurrent cases after chemotherapy were significantly higher than those not receiving chemotherapy. Meanwhile, expression of γ GCSh and MRP1 in carcinoma had a strong correlation ( r=0 786, P <0 01). It was concluded that the up regulation of γ GCSh and MRP 1 could be activated during carcinogenesis of bladder cancers; Overexpression of γ GCSh and MRP 1 might be an important factor inducing chemotherapy resistance of bladder cancers; A common regulatory way might existed in expression of γ GCSh and MRP 1.