Gaudino G, Cirillo D, Naldini L, Rossino P, Comoglio P M
Department of Biomedical Sciences and Oncology, University of Torino Medical School, Turin, Italy.
Proc Natl Acad Sci U S A. 1988 Apr;85(7):2166-70. doi: 10.1073/pnas.85.7.2166.
It has been hypothesized that bombesin-like peptides produced by small cell lung carcinomas may sustain deregulated proliferation through an autocrine mechanism. We have shown that the neuropeptide bombesin leads to the activation of a protein-tyrosine kinase that phosphorylates a 115-kDa protein (p115) associated with the bombesin receptor complex in mouse Swiss 3T3 fibroblasts. We now report that phosphotyrosine antibodies recognize a 115-kDa protein, phosphorylated on tyrosine, in four human small cell lung carcinoma cell lines producing bombesin but not in a nonproducer "variant" line. p115 from detergent-treated small cell lung carcinoma cells binds to bombesin-Sepharose and can be phosphorylated on tyrosine in the presence of radiolabeled ATP and Mn2+. As for the p115 immunoprecipitated from mouse fibroblast, the small cell lung carcinoma p115 can be phosphorylated in an immunocomplex kinase assay. However, the latter does not require the presence of exogenous bombesin for activity. Binding data, obtained by using radiolabeled ligand, suggest receptor occupancy in the cell lines producing bombesin. These observations are consistent with the hypothesis that proliferation in some human small cell lung carcinoma lines is under autocrine control, regulated through activation of bombesin receptors.
据推测，小细胞肺癌产生的蛙皮素样肽可能通过自分泌机制维持增殖失调。我们已经表明，神经肽蛙皮素可导致一种蛋白酪氨酸激酶的激活，该激酶使与小鼠瑞士3T3成纤维细胞中蛙皮素受体复合物相关的115 kDa蛋白（p115）磷酸化。我们现在报告，磷酸酪氨酸抗体可识别在四种产生蛙皮素的人小细胞肺癌细胞系中酪氨酸磷酸化的115 kDa蛋白，但在非产生性“变体”细胞系中则不能识别。来自经去污剂处理的小细胞肺癌细胞的p115与蛙皮素琼脂糖结合，并且在存在放射性标记的ATP和Mn2+的情况下可在酪氨酸上磷酸化。至于从小鼠成纤维细胞免疫沉淀的p115，小细胞肺癌p115可在免疫复合物激酶测定中被磷酸化。然而，后者的活性不需要外源性蛙皮素的存在。通过使用放射性标记配体获得的结合数据表明，在产生蛙皮素的细胞系中受体被占据。这些观察结果与以下假设一致，即某些人小细胞肺癌细胞系中的增殖受自分泌控制，通过蛙皮素受体的激活进行调节。
