The bmi-1 oncoprotein is differentially expressed in non-small cell lung cancer and correlates with INK4A-ARF locus expression.
The bmi-1 oncoprotein is differentially expressed in non-small cell lung cancer and correlates with INK4A-ARF locus expression.
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DOI：
10.1054/bjoc.2001.1791
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发表时间：
2001-05-18
影响因子：
8.8
通讯作者：
Betticher DC
中科院分区：
文献类型：
--
作者：
Vonlanthen S;Heighway J;Altermatt HJ;Gugger M;Kappeler A;Borner MM;van Lohuizen M;Betticher DC
多梳群的基因通过沉默调控胚胎发生的同源选择基因而起作用。在小鼠中，其中一种多梳基因bmi-1的下调会导致神经系统的改变和淋巴样细胞的严重增殖缺陷，而bmi-1的过表达和myc-1的上调会诱发淋巴瘤。原代成纤维细胞研究进一步支持了一种致癌功能，其中bmi-1过表达由于抑制p16/p19ARF而诱导永活，并且与H-ras一起容易转化mef。本研究的目的是评估bmi-1在可切除的非小细胞肺癌（NSCLC）中与p16和p14ARF（=人类p19ARF）的表达。肿瘤(48例可切除的非小细胞肺癌（32例鳞癌，9例腺癌，2例大细胞癌，4例未分化癌和1例类癌）；阶段1、29、II、7、III、12；T1, 18, t2, 30；分化：G1 12、G2 19、G3 17)，免疫组化检测蛋白表达，多重PCR检测基因扩增。在无肿瘤患者的正常肺组织中，在一些上皮细胞、淋巴细胞、腺细胞和成纤维细胞中可见弱-中度的bmi-1染色，而血液、内皮细胞、软骨细胞、肌肉细胞和脂肪细胞未表现出任何bmi-1表达。肿瘤中，恶性细胞阴性/弱阳性20例，中度阳性22例，强阳性6例。多重PCR结果显示，bmi-1基因扩增不是导致bmi-1高表达的原因。中度或强烈表达bmi-1的肿瘤更可能具有低水平的p16和p14ARF （P = 0.02）。同样，p16和p14ARF均阴性的肿瘤表现出中等强度的bmi-1染色。58%可切除的非小细胞肺癌表现出中高水平的bmi-1蛋白。bmi-1与INK4基因座蛋白表达（p16/p14ARF）的负相关支持了bmi-1失调在肺癌发生中的可能作用。©2001癌症研究运动www.bjcancer.com
Genes of the polycomb group function by silencing homeotic selector genes that regulate embryogenesis. In mice, downregulation of one of the polycomb genes, bmi-1, leads to neurological alterations and severe proliferative defects in lymphoid cells, whilst bmi-1 overexpression, together with upregulation of myc-1, induces lymphoma. An oncogenic function has been further supported in primary fibroblast studies where bmi-1 overexpression induces immortalization due to repression of p16/p19ARF, and where together with H-ras, it readily transforms MEFs. It was the aim of this study to assess the expression of bmi-1 in resectable non-small cell lung cancer (NSCLC) in association with p16 and p14ARF (=human p19ARF). Tumours (48 resectable NSCLC (32 squamous, 9 adeno-, 2 large cell, 4 undifferentiated carcinomas and 1 carcinoid); stage I, 29, II, 7, III, 12; T1, 18, T2, 30; differentiation: G1 12, G2 19, G3 17) were studied by immunohistochemistry for protein expression and by comparative multiplex PCR for gene amplification analysis. In tumour-free, normal lung tissue from patients, weak – moderate bmi-1 staining was seen in some epithelial cells, lymphocytes, glandular cells and in fibroblasts, whereas blood, endothelial, chondrocytes, muscle cells and adipocytes did not exhibit any bmi-1 expression. In tumours, malignant cells were negative/weakly, moderately and strongly positive in 20, 22 and 6 cases, respectively. As assessed by multiplex PCR, bmi-1 gene amplification was not the reason for high-level bmi-1 expression. Tumours with moderate or strong bmi-1 expression were more likely to have low levels of p16 and p14ARF (P = 0.02). Similarly, tumours negative for both, p16 and p14ARF, exhibit moderate–strong bmi-1 staining. 58% of resectable NSCLC exhibit moderate–high levels of bmi-1 protein. The inverse correlation of bmi-1 and the INK4 locus proteins expression (p16/p14ARF) supports a possible role for bmi-1 misregulation in lung carcinogenesis. © 2001 Cancer Research Campaign www.bjcancer.com
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影响因子：
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