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

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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.