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Ubc9,一种单一的小泛素样修饰物(SUMO)E2 连接酶,在正常组织和恶性组织中的表达分析。

Expression analysis of Ubc9, the single small ubiquitin-like modifier (SUMO) E2 conjugating enzyme, in normal and malignant tissues.

机构信息

Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA.

出版信息

Hum Pathol. 2010 Sep;41(9):1286-98. doi: 10.1016/j.humpath.2010.02.007. Epub 2010 Jun 18.

Abstract

Unlike ubiquitination, which targets proteins for degradation, sumoylation modulates protein-protein interactions of target proteins. Although there are multiple E2 enzymes required for ubiquitination, there is only one E2-conjugating enzyme for sumoylation, which is Ubc9. In line with increasing evidence that sumoylation plays an important role in tumorigenesis, we recently demonstrated that Ubc9 is expressed at high levels in advanced melanomas and that blocking expression of Ubc9 sensitizes melanomas to the cytotoxic effects of chemotherapeutic drugs. To determine whether and to what extent Ubc9 is expressed in other malignancies and their normal tissue counterparts, we undertook a detailed analysis of colon, lung, prostate, and breast cancer tissue microarrays. The findings, presented here, document that in primary colon and prostate cancer, Ubc9 expression is increased compared with their normal tissue counterparts, whereas in metastatic breast, prostate, and lung cancer, it is decreased in comparison with their corresponding normal and primary adenocarcinoma tissues. We also provide evidence that Ubc9 expression correlates positively with Dukes' stage and negatively with the Gleason score as well as breast cancer grade and that Ubc9 expression is substantially higher in the luminal than in the nonluminal type of breast cancer.

摘要

与将蛋白质靶向降解的泛素化不同,SUMO 化修饰调节靶蛋白的蛋白质-蛋白质相互作用。虽然泛素化需要多种 E2 酶,但 SUMO 化只有一种 E2 连接酶,即 Ubc9。越来越多的证据表明 SUMO 化在肿瘤发生中起着重要作用,我们最近证明 Ubc9 在晚期黑色素瘤中高表达,并且阻断 Ubc9 的表达使黑色素瘤对化疗药物的细胞毒性作用敏感。为了确定 Ubc9 是否以及在何种程度上在其他恶性肿瘤及其正常组织对应物中表达,我们对结肠癌、肺癌、前列腺癌和乳腺癌组织微阵列进行了详细分析。这里呈现的研究结果表明,在原发性结肠癌和前列腺癌中,与相应的正常组织相比,Ubc9 的表达增加,而在转移性乳腺癌、前列腺癌和肺癌中,与相应的正常和原发性腺癌组织相比,Ubc9 的表达降低。我们还提供了证据表明,Ubc9 的表达与 Dukes 分期呈正相关,与 Gleason 评分以及乳腺癌分级呈负相关,并且在腔型乳腺癌中 Ubc9 的表达明显高于非腔型乳腺癌。

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