Gene Expression Analysis of the 26S Proteasome Subunit PSMB4 Reveals Significant Upregulation, Different Expression and Association with Proliferation in Human Pulmonary Neuroendocrine Tumours.
Gene Expression Analysis of the 26S Proteasome Subunit PSMB4 Reveals Significant Upregulation, Different Expression and Association with Proliferation in Human Pulmonary Neuroendocrine Tumours.
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DOI：
10.7150/jca.9955
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发表时间：
2014
影响因子：
3.9
通讯作者：
Wohlschlaeger J
中科院分区：
文献类型：
--
作者：
Mairinger FD;Walter RF;Theegarten D;Hager T;Vollbrecht C;Christoph DC;Worm K;Ting S;Werner R;Stamatis G;Mairinger T;Baba H;Zarogoulidis K;Huang H;Li Q;Tsakiridis K;Zarogoulidis P;Schmid KW;Wohlschlaeger J
背景：蛋白酶体亚基PSMB4在肝细胞癌动物模型和胶质母细胞瘤细胞系中被认为是一个存活基因。在肺腺癌中，这些基因的高表达被发现与低分化和生存有关。本研究探讨了26S蛋白酶体亚基在人肺神经内分泌肿瘤（包括典型（TC）和非典型（AC）类癌以及小细胞（SCLC）和大细胞（LCNEC）神经内分泌癌）中的基因表达水平。材料与方法：研究80例神经内分泌肺肿瘤（TC、AC、LCNLC和SCLC各20例）中蛋白酶体亚基（PSMA1、PSMA5、PSMB4、PSMB5和PSMD1）的基因表达水平，并与对照组进行比较。采用TaqMan法测定mRNA水平。采用组织微阵列（TMA）免疫组化检测ki67、cleaved caspase 3和PSMB4的表达。结果：与对照组相比，TC、AC、SCLC和LCNEC的所有蛋白酶体亚基基因表达均显著上调。PSMB4 mRNA在所有神经内分泌肿瘤亚型中表达不同，在LCNEC中表达最高，范围最大（p=0.043），并与增殖活性显著相关（p=0.039）。结论：PSMB4与其他26S蛋白酶体亚基一致显著升高，但在肺神经内分泌肿瘤中表达不同，且与增殖活性相关。与肺腺癌不同，没有观察到与生物学行为的关联，这表明蛋白酶体亚基基因表达的增加是肺神经内分泌肿瘤发生的常见和可能的早期事件，无论其分化如何。
Background: Proteasomal subunit PSMB4 was suggested to be a survival gene in an animal model of hepatocellular carcinoma and in glioblastoma cell lines. In pulmonary adenocarcinoma, a high expression of these genes was found to be associated with poor differentiation and survival. This study investigates the gene expression levels of 26S proteasome subunits in human pulmonary neuroendocrine tumours including typical (TC) and atypical (AC) carcinoid tumours as well as small cell (SCLC) and large cell (LCNEC) neuroendocrine carcinomas. Material and methods: Gene expression levels of proteasomal subunits (PSMA1, PSMA5, PSMB4, PSMB5 and PSMD1) were investigated in 80 neuroendocrine pulmonary tumours (each 20 TC, AC, LCNLC and SCLC) and compared to controls. mRNA levels were determined by using TaqMan assays. Immunohistochemistry on tissue microarrays (TMA) was performed to determine the expression of ki67, cleaved caspase 3 and PSMB4. Results: All proteasomal subunit gene expressions were significantly upregulated in TC, AC, SCLC and LCNEC compared to controls. PSMB4 mRNA is differently expressed between all neuroendocrine tumour subtypes demonstrating the highest expression and greatest range in LCNEC (p=0.043), and is significantly associated with proliferative activity (p=0.039). Conclusion: In line with other 26S proteasomal subunits PSMB4 is significantly increased, but differently expressed between pulmonary neuroendocrine tumours and is associated with the proliferative activity. Unlike in pulmonary adenocarcinomas, no association with biological behaviour was observed, suggesting that increased proteasomal subunit gene expression is a common and probably early event in the tumorigenesis of pulmonary neuroendocrine tumours regardless of their differentiation.
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