Changes of cytokines and their gene expression in the process of carcinogenesis of oral precancerous lesions

我们研究了从癌前病变或癌前状态（如白斑和乳头状瘤）中获得的癌症患者标本中细胞因子的定位及其基因表达。同时测定癌变前后朗格汉斯细胞（LC）和HLA-DR抗原阳性LC数量的变化。进一步，我们测试了细胞因子（tnf - α、tgf - β、ifn - γ）或它们的组合对口腔癌细胞系（NA）细胞增殖的影响，并估计了细胞增殖与原癌基因（c-myc、ras）表达之间的关系。实验结果如下：1。tgf - α的定位随着癌症的发展而增加，而tgf - β的定位随着癌变而减少。tgf - α的升高与PCNA的升高有良好的相关性，PCNA被认为是细胞增殖的良好标志。tgf - α mRNA的表达随癌变而升高。LC和HLA-DR抗原阳性LC的数量随致癌性的增加而增加。tnf - α与tgf - β或tnf - α与ifn - γ联合抑制NA细胞增殖。细胞增殖的抑制似乎是通过下调c-myc mRNA的表达来实现的。

We investigated localization of cytokines and the expression of their genes in the specimens that were obtained from cancer patients whose cancer resions were developed from precancerous lesions or status, such as leukoplakia and papiloma. Changes of the numbers of Langerhans cells (LC) and HLA-DR antigen positive LC were also estimated before and after carcinogenesis. Further, the effect of cytokines (TNF-alpha, TGF-beta, IFN-gamma) or their combinations on cell proliferation of a oral cancer cell line (NA) was tested and the relationship between cell proliferation and the expression of protooncogenes (c-myc, ras) was estimated.The results obtained were as follows :1.The localization of TGF-alpha was increased with development to cancer, whereas TGF-beta was decreased with carcinogenesis. The increase of TGF-alpha was well correlated with that of PCNA which is now thought to be good marker of cell proliferation.2.The Expression of TGF-alpha mRNA was increased with carcinogenesis.3.The numbers of LC and HLA-DR antigen positive LC were increased with carcinogenesis.4.The combination of TNF-alpha and TGF-beta or TNF-alpha and IFN-gamma inhibited cell proliferation of NA cells aditively or synergistically. The inhibition of cell proliferaton seemed to be brought about by the downregulation of c-myc mRNA expression.