Imaizumi M, Nishimura M, Takeuchi S, Murase M, Hamaguchi M
Department of Thoracic Surgery, Nagoya University School of Medicine, Japan.
Lung Cancer. 1997 May;17(1):69-84. doi: 10.1016/s0169-5002(97)00650-8.
To clarify the role of tyrosine phosphorylation of cellular proteins in human lung cancer cells, phosphotyrosine (PTYR)-containing proteins in lung cancer cell lines and in paired tissues resected from cancerous and normal lungs were studied by immunoblotting with an anti-PTYR antibody. We found that the profiles of protein phosphorylation were very similar among those cell lines which had different histological features. The major PTYR-containing proteins (180-190 KDa, 120-130 KD, and 95-100 KDa) were detected in lung cancer cell lines. The expression of EGF receptor (EGF-r) (p185) and o-erb B2 protein, and tyrosine phosphorylation of p125FAK were examined in cancerous lung tissues and normal lung tissues. 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 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 phosphorylation 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 plays 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.
为阐明细胞蛋白酪氨酸磷酸化在人肺癌细胞中的作用，我们用抗磷酸酪氨酸（PTYR）抗体进行免疫印迹，研究了肺癌细胞系以及取自癌肺和正常肺的配对组织中含磷酸酪氨酸（PTYR）的蛋白。我们发现，具有不同组织学特征的细胞系之间，蛋白磷酸化谱非常相似。在肺癌细胞系中检测到主要的含PTYR蛋白（180 - 190 kDa、120 - 130 kDa和95 - 100 kDa）。检测了癌肺组织和正常肺组织中表皮生长因子受体（EGF - r）（p185）和o - erb B2蛋白的表达以及p125FAK的酪氨酸磷酸化。在手术标本中，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和c - erb B2蛋白表达的明显扩增。然而，在癌肺组织中观察到p125FAK的酪氨酸磷酸化升高，而在正常肺组织中未观察到，其磷酸化与癌症的淋巴结受累和无病生存期密切相关。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永生化中起作用，评估细胞蛋白的酪氨酸磷酸化，尤其是p125FAK，可能在临床上作为一种预后因素。
