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人胶质瘤中STK15的过表达与扩增

Overexpression and amplification of STK15 in human gliomas.

作者信息

Klein Alexandra, Reichardt Wilfried, Jung Volker, Zang Klaus D, Meese Eckart, Urbschat Steffi

机构信息

Institute of Human Genetics, Saarland University, Building 60, D-66421 Homburg/Saar, Germany.

出版信息

Int J Oncol. 2004 Dec;25(6):1789-94.

Abstract

The serine/threonine kinase 15 (STK15) at chromosome 20q13.2 is frequently shown to be amplified and overexpressed in several human cancers. STK15 has been reported to act as a cell cycle regulator and its overexpression induces centrosome amplification and aneuploidy. Recently we showed that STK15 even plays a role in human malignant brain tumours and we described an amplification of the gene in 31% of the investigated gliomas. In this study we scrutinized the correlation of increased STK15 on DNA and mRNA levels in gliomas of different histological grades. Southern blotting confirmed the amplification frequency of the STK15 gene, which had been previously detected by comparative PCR. In total, DNA gains were found in 26% of the investigated gliomas. Interestingly, we detected overexpression of STK15 mRNA in 60% of the analyzed brain tumours. The elevated expression does not strongly correlate with gains on DNA level, but all cases with an amplification of the STK15 gene display overexpression. Gains of the STK15 gene seem to occur irrespectively of the histological grades of the tumours, so that STK15 probably is not a progression associated factor. Amplification and overexpression of the kinase rather represent a primary alteration in human gliomas, which could play an important role as an early event in all glioma subtypes.

摘要

位于20号染色体q13.2区域的丝氨酸/苏氨酸激酶15(STK15)在多种人类癌症中常表现出扩增和过表达。据报道,STK15作为一种细胞周期调节因子,其过表达会导致中心体扩增和非整倍体。最近我们发现STK15在人类恶性脑肿瘤中也发挥作用,并且在31%的被研究胶质瘤中发现了该基因的扩增。在本研究中,我们仔细研究了不同组织学分级的胶质瘤中STK15在DNA和mRNA水平增加之间的相关性。Southern印迹法证实了STK15基因的扩增频率,这一频率先前已通过比较PCR检测到。总共在26%的被研究胶质瘤中发现了DNA增加。有趣的是,我们在60%的分析脑肿瘤中检测到STK15 mRNA的过表达。表达升高与DNA水平的增加并没有很强的相关性,但所有STK15基因扩增的病例均表现出过表达。STK15基因的增加似乎与肿瘤的组织学分级无关,因此STK15可能不是一个与肿瘤进展相关的因素。该激酶的扩增和过表达更可能代表人类胶质瘤中的一种原发性改变,这可能作为所有胶质瘤亚型的早期事件发挥重要作用。

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