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首页> 外文期刊>Journal of Pathology: Journal of the Pathological Society of Great Britain and Ireland >Deregulated Bag-1 protein expression in human oral squamous cell carcinomas and lymph node metastases.
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Deregulated Bag-1 protein expression in human oral squamous cell carcinomas and lymph node metastases.

机译：Bag-1蛋白在人口腔鳞状细胞癌和淋巴结转移中的表达失调。

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摘要

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-1s, Bag-1M, and Bag-1L were expressed in normal and malignant oral epithelial cells. Bag-1L unique sequences were shown to adopt an exclusively nuclear, and predominantly nucleolar, localization by use of transiently transfected N-terminal Bag-1L-EGFP. However, levels of Bag-1L 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-1L. Alterations in the relative proportions of Bag-1S, Bag-1M, and Bag-1L were detected in 6/9 oral carcinoma cell lines; 5/9 oral carcinoma cell lines had a significantly greater proportion of Bag-1M than normal keratinocytes and in another cell line, Bag-1L 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.
机译：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种口腔鳞状细胞癌中是否发生改变，将肿瘤样本与正常口腔上皮的17种样本进行了比较。正常的口腔上皮在基底层和成熟层具有明显的核染色，而在基底层和基底上层具有最明显的弱细胞质染色。口腔鳞状细胞癌显示出核染色强度降低的趋势（p = 0.036）。肿瘤与正常组织之间的细胞质染色强度无明显差异。然而，观察到许多肿瘤与正常口腔上皮相比在核染色强度和细胞质染色强度之间的差异较小。此外，在淋巴结转移中，与相应的原发肿瘤相比，在8/13例中细胞质Bag-1染色更强（p = 0.021）。使用9种口腔原发癌细胞系和4种正常角质形成细胞培养物进行的蛋白质印迹显示，同型亚型Bag-1s，Bag-1M和Bag-1L在正常和恶性口腔上皮细胞中表达。通过使用瞬时转染的N末端Bag-1L-EGFP，Bag-1L独特序列被证明具有唯一的核定位，并且主要是核仁定位。但是，癌细胞中Bag-1L的水平与正常角质形成细胞没有显着差异。因此，与正常上皮相比，口腔鳞状细胞癌中观察到的核染色减少可能反映了Bag-1同工型的定位变化，而不是Bag-1L表达下降。在6/9口腔癌细胞系中检测到Bag-1S，Bag-1M和Bag-1L的相对比例发生了变化。 5/9口腔癌细胞系中Bag-1M的比例明显高于正常角质形成细胞，而在另一种细胞系中，Bag-1L的代表性明显不足。总体而言，结果表明Bag-1失调在口腔癌变过程中的两个不同阶段均起作用：在原发癌发展过程中和淋巴结转移过程中。

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