核转录因子-κB在金地鼠颊囊癌变过程中的表达研究

Expression of Nuclear Transcription Factor κB in Hamster Buccal Pouch Carcinogenesis

目的探讨核转录因子-κB家族成员的重要亚基p65及其抑制蛋白IκBα在金地鼠颊囊鳞癌发生过程中的表达及意义。方法建立金地鼠颊囊癌变的动物模型,采用Western blot法检测金地鼠正常颊黏膜、上皮单纯增生黏膜、上皮异常增生黏膜和鳞癌组织所提取的核蛋白中p65的表达差异;采用SABC免疫组织化学法检测在金地鼠颊黏膜正常上皮、上皮单纯增生、上皮异常增生、鳞状细胞癌中IκBα的表达变化。结果正常黏膜和上皮单纯增生黏膜中,p65表达很弱,但普遍存在IκBα的表达,该表达多局限于黏膜基底层和棘层底部细胞的胞浆中。随着上皮异常增生的出现,p65表达增强,与正常黏膜和单纯增生黏膜相比有统计学意义(P<0.01),而IκBα表达则显著下降(P<0.05)。鳞癌组织中p65的表达显著高于正常黏膜和异常增生黏膜(P<0.01),IκBα的表达显著升高,明显高于上皮异常增生黏膜(P<0.01),甚至超过正常水平(P<0.01)。结论p65在金地鼠颊囊鳞癌发生、发展过程中被激活。p65和IκBα在金地鼠颊囊癌变过程中的表达异常,上皮异常增生阶段p65的表达上调而IκBα的表达下调,可能是口腔黏膜上皮癌变过程中的早期事件,可作为口腔早期癌变监测的生物学指标。

Objective To study the expression and significance of 1365 which is an important subtype of nuclear transcription factor κB （NF-κB） and its inhibitory protein IxBa in malignant transformation of hamster buccal mucosa. Methods The animal model of malignant transformation in hamster buccal mucosa induced by DMBA（0.5%） was established. Twelve paired specimens including normal buccal mucosa, epithelial hyperplasia, epithelial dysplasia and squamous cell carcinoma （SCC） were subjected to Western blot for the analysis of p65 .The expression of IxBa was observed in 22 normal buccal epithelia, 20 hyperplasia epithelia,35 dysplasia epithelia and 23 SCC by immunohistochemical evaluation. Results In normal buccal epithelia and hyperplasia epithelia, the expression of p65 was not obvious, and there was no significant difference between them（P 〉 0.05） .The expression of IκBα existed at large, but mostly localizing in cell cytoplasmic staining in the basal cell layer and bottom of spinocelluar layer.With the occurrence of epithelia dysplasia, the expression of p65 gradually increased, comparing with normal buccal epithelia and hyperplasia epithelia（ P 〈 0.01）. But the positive intensity of IxBa was dramatically decreased（ P 〈 0.05 ）. In SCC, p65 expressed at a higher level comparing with normal buccal mucosa and dysplasia（ P 〈 0.01）, while the staining of IxBa was feedbackly higher comparing with dysplasia（ P 〈 0.01 ） and even with normal buccal mucosa（ P 〈 0.01 ）. Conclusion NF-κB p65 is strongly activated in malignant transformation of hamster buccal mucosa. The abnormal expression of p65 and IxBa,especially the ascending expression of p65 as well as the descending expression of IxBa in dysplasia may be an early event during oral carcinogenesis, and can be used as biomarkers for supervising oral malignancy.