The role of flbroblasts against tyrosine specific phosphorylatlon of cellular proteins in human lung cancer cells and nodal lnvolvement of cancer

我们研究的目的是阐明成纤维细胞在人肺癌细胞中对细胞蛋白酪氨酸磷酸化的作用，以及淋巴结的参与。我们发现，与EGF作用相似的生长促进因子从成纤维细胞中释放出来，当EGF处理一些肺癌细胞时，这些细胞中酪氨酸特异性磷酸化明显增加。在不同组织学特征的肺癌细胞系中，我们发现含有磷酸酪氨酸（PTYR）的蛋白谱非常相似，在肺癌细胞系中检测到主要的含PTYR蛋白（180 ~ 190kda: EGF-r (p185)， 120 ~ 130kd: p125FAK和95 ~ 100kda）。在手术标本中，大约一半的肺癌组织样本显示酪氨酸磷酸化明显升高。在这些癌组织中，未观察到EGF-r （p185）和c- erbb B2蛋白表达的明显扩增。然而，p125FAK酪氨酸磷酸化水平在癌性肺组织中升高，而在正常肺组织中未见升高，且其磷酸化水平与肿瘤的淋巴结累及及无病生存时间密切相关。这些结果表明，通过酪氨酸磷酸化的细胞内信号通路在肺癌的发生和不朽中发挥作用，并且评估酪氨酸磷酸化的细胞蛋白，特别是p125FAK，可能在临床上作为预后因素。

The purpose of our study is to clarify the role of fibroblasts against tyrosine phosphorylation of cellular proteins in human lung cancer cells, and nodal involvement. We found that the growthpromoting factor with action similar to that of EGF was released from fibroblasts and when some lung cancer cells were treated with EGF,tyrosine specific phosphorylation in these cells clearly increased. And then we found that the profiles of phosphotyrosine (PTYR)-containing protein were very similar among lung cancer cell lines which had different histological features, The major PTYR-contaning proteins (180-190KDa : EGF-r (p185), 120-130KD : p125FAK and 95-100KDa) were detected in lung cancer cell lines. In surgical specimens, approximately half of the samples of lung cancer tissues showed clear elevation of tyrosine phosphorylation. In these cancerous tissues, no clear amplification of EGF-r (p185) and c-erb B2 protein expression was observed. However, elevation of tyrosine phosphorylation of p125FAK was observed in cancerous lung tissues but not in normal lung tissues, and its phosohorylation was closely correlated with the nodal involvement of cancer and disease free survival time. These results suggested that the intracellular signaling pathway via tyrosine phosphorylation play a role in the generation and immortalization of lung cancer, and assessment of tyrosine phosphorylation of cellular proteins, especially p125FAK,may be available clinically as a prognostic factor.