Over-expression of genes and proteins of ubiquitin specific peptidases (USPs) and proteasome subunits (PSs) in breast cancer tissue observed by the methods of RFDD-PCR and proteomics

Over-expression of genes and proteins of ubiquitin specific peptidases (USPs) and proteasome subunits (PSs) in breast cancer tissue observed by the methods of RFDD-PCR and proteomics
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DOI:
10.1007/s10549-006-9393-7
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发表时间:
2007-07-01
影响因子:
3.8
通讯作者:
Yang, Huijun
Yang, Huijun
中科院分区:
医学2区
文献类型:
--
作者:
Deng, Shishan;Zhou, Hongying;Yang, Huijun

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泛素-蛋白酶体系统促进受损蛋白质的降解以及生长和应激反应的调节。这种蛋白水解系统的改变与多种人类病理学有关。通过限制性片段差异显示聚合酶链反应(RFDD-PCR)和基质辅助激光解吸电离串联飞行时间质谱(MALDI-TOF-TOF MS)基于二维聚丙烯酰胺凝胶电泳(2-DE)、泛素特异性蛋白酶(USP)的差异表达基因和蛋白,分析了乳腺癌组织和癌旁正常组织中蛋白酶体亚单位(PS)和泛素蛋白连接酶E3A(UBE 3A)的表达。免疫组化染色证实部分细胞为过表达.其中5个蛋白酶体亚基(PSs)基因(PSMB 5、PSMD 1、PSMD 2、PSMD 8和PSMD 11)、4个USP基因(USP 9X、USP 9Y、USP 10和USP 25)和泛素蛋白连接酶E3A(UBE 3A)基因在大肠杆菌中过表达在乳腺癌组织中观察到PSMA 1和SMT3A蛋白的过表达(> 3倍),并且在乳腺癌组织中观察到PSMA 1和SMT3A蛋白的过表达(> 4倍)。免疫组化染色进一步证实PSMD 8、PSMD 11和UBE 3A为高表达。泛素-蛋白酶体系统在乳腺癌中的作用明显增强,选择性干预泛素-蛋白酶体系统的作用可能是治疗乳腺癌的有效方法。
The ubiquitin - proteasome system facilitates the degradation of damaged proteins and regulators of growth and stress response. Alterations in this proteolytic system are associated with a variety of human pathologies. By restriction fragment differential display polymerase chain reaction ( RFDD- PCR) and matrix- assisted laser desorption/ ionization tandem time- of- flight mass spectrometry ( MALDI- TOF- TOF MS) based on two- dimensional polyacrylamide gel electrophoresis ( 2- DE), differentially expressed genes and proteins of ubiquitin specific proteases ( USPs), proteasome subuinits ( PSs) and ubiquitin protein ligase E3A ( UBE3A) were analyzed between breast cancer and adjacent normal tissues. Some of them were further verified as over- expression by immunohistochemical stain. Five genes of proteasome subunits ( PSs), including PSMB5, PSMD1, PSMD2, PSMD8 and PSMD11, four genes of USPs, including USP9X, USP9Y, USP10 and USP25, and ubiquitin protein ligase E3A ( UBE3A) were over- expressed (> 3- fold) in breast cancer tissue compared to adjacent normal tissue, and over- expression (> 4- fold) of proteins of PSMA1 and SMT3A were observed in breast cancer tissue. PSMD8, PSMD11 and UBE3A were further verified as over- expression by immunohistochemical stain. The action of ubiquitin - proteasome system were obviously enhanced in breast cancer, and selectively intervention in action of ubiquitin - proteasome system may be a useful method of treating human breast cancer.