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

本研究的目的是阐明成纤维细胞对人肺癌细胞中细胞蛋白酪氨酸磷酸化的作用，以及淋巴结受累。我们发现成纤维细胞释放出与EGF作用相似的促生长因子，当用EGF处理某些肺癌细胞时，这些细胞的酪氨酸特异性磷酸化明显增加。结果发现，不同组织学特征的肺癌细胞株中，PTYR蛋白表达谱非常相似，主要表达180- 190 KDa：EGF-r（p185），120- 130 KDa：p125 FAK和95- 100 KDa的PTYR蛋白。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，没有观察到明显的EGF-r（p185）和c-erb B2蛋白表达的扩增。p125 FAK酪氨酸磷酸化水平在肺癌组织中升高，而在正常肺组织中无明显变化，且与肺癌淋巴结转移和无病生存期密切相关。这些结果提示，细胞内酪氨酸磷酸化信号通路在肺癌的发生和永生化过程中起重要作用，检测细胞蛋白尤其是p125 FAK的酪氨酸磷酸化水平，可作为临床上判断肺癌预后的指标。

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.