Deregulated Bag-1 protein expression in human oral squamous cell carcinomas and lymph node metastases
Deregulated Bag-1 protein expression in human oral squamous cell carcinomas and lymph node metastases
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DOI：
10.1002/path.1076
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发表时间：
2002-05-01
影响因子：
7.3
通讯作者：
Eveson, JW
中科院分区：
文献类型：
--
作者：
Hague, A;Packham, G;Eveson, JW
Bag-1 是一种抗凋亡蛋白，可促进某些肿瘤细胞类型的转移。为了确定 Bag-1 表达在 64 例口腔鳞状细胞癌中是否发生改变，将肿瘤样本与 17 例正常口腔上皮样本进行了比较。正常口腔上皮在基底层和成熟层具有明显的核染色，而弱细胞质染色在基底层和基底上层最为明显。口腔鳞状细胞癌表现出核染色强度降低的趋势（p = 0.036）。肿瘤组织和正常组织之间的细胞质染色强度没有显着差异。然而，观察到许多肿瘤的核染色强度和细胞质染色强度之间的差异小于正常口腔上皮。此外，在淋巴结转移中，8/13例的细胞质Bag-1染色强于相应的原发肿瘤（P=0.021）。使用九种口腔原发癌细胞系和四种正常角质形成细胞培养物进行的蛋白质印迹显示，同工型 Bag-1(S)、Bag-1(M) 和 Bag-1(L) 在正常和恶性口腔上皮细胞中表达。 Bag-1(L) 是一种独特的序列，通过使用瞬时转染的 N 端 Bag-1(L)-EGFP，仅进行核定位，并且主要定位于核仁。然而，癌细胞中 Bag-1(L) 的水平与正常角质形成细胞中的水平没有显着差异。因此，与正常上皮相比，在口腔鳞状细胞癌中观察到的核染色减少可能反映了 Bag-1 同种型定位的变化，而不是 Bag-1(L) 表达的减少。在6/9口腔癌细胞系中检测到Bag-1(S)、Bag-1(M)和Bag-1(L)相对比例的改变； 519 口腔癌细胞系的 Bag-1(M) 比例明显高于正常角质形成细胞，而在另一种细胞系中，Bag-1(L) 的比例明显不足。总体而言，结果表明 Bag-1 失调在两个不同阶段的口腔癌发生中发挥作用：原发癌发展期间和淋巴结转移期间。版权所有 (C) 2002 John Wiley Sons, Ltd.
Bag-1 is an anti-apoptotic protein that promotes metastasis in some tumour cell types. To determine whether Bag-1 expression is altered in 64 oral squamous cell carcinomas, tumour samples were compared with 17 samples of normal oral epithelium. Normal oral epithelia had pronounced nuclear staining in the basal and maturation layers and weak cytoplasmic staining that was most pronounced in the basal and suprabasal layers. Oral squamous cell carcinomas demonstrated a tendency for reduced nuclear staining intensity (p = 0.036). Cytoplasmic staining intensity was not significantly different between tumour and normal tissue. However, many tumours were observed to have less of a difference between nuclear staining intensity and cytoplasmic staining intensity than normal oral epithelium. Furthermore, in lymph node metastases, cytoplasmic Bag-1 staining was stronger in 8/13 cases than in corresponding primary tumours (P=0.021). Western blotting using nine oral primary carcinoma cell lines and four normal keratinocyte cultures showed that the isoforms Bag-1(S), Bag-1(M), and Bag-1(L) were expressed in normal and malignant oral epithelial cells. Bag-1(L), unique sequences were shown to adopt an exclusively nuclear, and predominantly nucleolar, localization by use of transiently transfected N-terminal Bag-1(L)-EGFP. However, levels of Bag-1(L) in carcinoma cells did not differ significantly from those of normal keratinocytes. Therefore the reduced nuclear staining observed in oral squamous cell carcinomas compared with normal epithelium may reflect changes in the localization of Bag-1 isoforms, rather than decreased expression of Bag-1(L). Alterations in the relative proportions of Bag-1(S), Bag-1(M), and Bag-1(L) were detected in 6/9 oral carcinoma cell lines; 519 oral carcinoma cell lines had a significantly greater proportion of Bag-1(M) than normal keratinocytes and in another cell line, Bag-1(L) was significantly underrepresented. Overall, the results suggest that Bag-1 deregulation plays a role in oral carcinogenesis at two different stages: during primary carcinoma development and during lymph node metastasis. Copyright (C) 2002 John Wiley Sons, Ltd.