Gene expression of O-GlcNAc cycling enzymes in human breast cancers.

Gene expression of O-GlcNAc cycling enzymes in human breast cancers.
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DOI:
10.1007/s10238-011-0138-5
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发表时间:
2012-03
影响因子:
4.6
通讯作者:
Brys, Magdalena
Brys, Magdalena
中科院分区:
医学3区
文献类型:
--
作者:
Krzeslak, Anna;Forma, Ewa;Bernaciak, Magdalena;Romanowicz, Hanna;Brys, Magdalena

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o - glcn酰化是一种丰富的、动态的、可诱导的翻译后修饰,其中单个β- n -乙酰氨基葡萄糖胺残基通过o -糖苷键连接到丝氨酸或tre氨酸残基上。提示异常调节的o - glcn酰化可能与肿瘤病理有关。O-GlcNAc残基在细胞内蛋白上的循环由两种酶控制,一种是O-GlcNAc转移酶(OGT),它催化O-GlcNAc残基的添加,另一种是核质β- n -乙酰氨基葡萄糖酶(O-GlcNAcase,由MGEA5基因编码),参与O-GlcNAc的去除。本研究分析了乳腺导管癌中O-GlcNAc循环酶编码基因mRNA表达与临床病理参数的关系。结果显示,低分化肿瘤(II级和III级)的OGT表达明显高于I级肿瘤。相反,与I级肿瘤相比,II级和III级肿瘤的MGEA5转录水平明显较低。Spearman秩相关分析显示,OGT与MGEA5在乳腺癌中的表达呈负相关(r = - 0.430, P = 0.0002)。淋巴结转移状态与mgea5mrna表达降低显著相关。这一结果表明,O-GlcNAc修饰蛋白的升高可能与乳腺肿瘤的进展和转移有关。
O-GlcNAcylation is an abundant, dynamic, and inducible posttranslational modification in which single β-N-acetylglucosamine residues are attached by O-glycosidic linkage to serine or treonine residues. It is suggested that abnormally regulated O-GlcNAcylation may contribute to the pathology of cancer. Cycling of O-GlcNAc residues on intracellular proteins is controlled by two enzymes, O-GlcNAc transferease (OGT), which catalyses the addition of O-GlcNAc residues and nucleocytoplasmic β-N-acetylglucosaminidase (O-GlcNAcase; encoded by MGEA5 gene), an enzyme involved in the removal of O-GlcNAc. In this study, relationship between the mRNA expressions of genes coding O-GlcNAc cycling enzymes in breast ductal carcinomas and clinicopathological parameters were analyzed. The results showed that poorly differentiated tumors (grade II and III) had significantly higher OGT expression than grade I tumors. Contrary, MGEA5 transcript levels were significantly lower in grade II and III in comparison with grade I tumors. The Spearman rank correlation showed the expressions of OGT and MGEA5 in breast cancer was negatively correlated (r = −0.430, P = 0.0002). Lymph node metastasis status was significantly associated with decreased MGEA5 mRNA expression. This result suggests that elevation in O-GlcNAc modification of proteins may be implicated in breast tumor progression and metastasis.
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