Su L, Morgan P R, Lane E B
Department of Oral Medicine and Pathology, United Medical School, Guy's Hospital, London, United Kingdom.
Am J Pathol. 1994 Dec;145(6):1349-57.
Simple epithelial keratins K7, K8, and K18 are present in no more than trace amounts in normal stratified squamous epithelial but have been reported in squamous cell carcinomas. With the aim of determining the level at which keratin synthesis is regulated in vivo, we have compared the expression of mRNA by in situ hybridization and protein by immunohistochemistry for K7, K8, and K18 in a series of normal, dysplastic, and malignant oral epithelia. In normal epithelia mRNAs for K7, K8, and K18 were present in basal and lower spinous cells but adjacent sections were generally negative for the respective proteins. In severe dysplasia there was irregular suprabasal extension of K8 and K18 mRNAs in all cases and their proteins were expressed in more than half of the cases. The carcinomas expressed K8 and K18 mRNAs homogeneously and were strongly reactive for these keratin proteins but K7 expression appeared reduced in malignancy. These results are consistent with the post-transcriptional regulation of K7, K8, and K18 expression in normal epithelia and the presence of their proteins in dysplastic and malignant epithelia suggests the release of these epithelial cells from a post-transcriptional block on K8 and K18 translation. Alternatively, rapid degradation of K8 and K18 protein might be occurring in normal epithelia but be suppressed in dysplasia and malignancy.
简单上皮角蛋白K7、K8和K18在正常复层鳞状上皮中含量不超过微量，但在鳞状细胞癌中已有报道。为了确定角蛋白合成在体内的调控水平，我们通过原位杂交比较了K7、K8和K18的mRNA表达，并通过免疫组织化学比较了它们在一系列正常、发育异常和恶性口腔上皮中的蛋白质表达。在正常上皮中，K7、K8和K18的mRNA存在于基底细胞和棘层下部细胞中，但相邻切片中相应蛋白质通常呈阴性。在重度发育异常中，所有病例中K8和K18的mRNA均有不规则的基底层以上延伸，且半数以上病例中表达了它们的蛋白质。癌组织中K8和K18的mRNA均匀表达，对这些角蛋白呈强阳性反应，但K7的表达在恶性肿瘤中似乎降低。这些结果与正常上皮中K7、K8和K18表达的转录后调控一致，而它们的蛋白质在发育异常和恶性上皮中的存在表明这些上皮细胞从K8和K18翻译的转录后阻滞中释放出来。或者，K8和K18蛋白可能在正常上皮中快速降解，但在发育异常和恶性肿瘤中受到抑制。
