Ruggiero M, Srivastava S K, Fleming T P, Ron D, Eva A
Laboratory of Cellular and Molecular Biology, National Cancer Institute, Bethesda, Maryland 20892.
Oncogene. 1989 Jun;4(6):767-71.
We have examined polyphosphoinositide turnover in mouse fibroblasts (NIH3T3) transformed by the dbl oncogene as compared to normal cells. The dbl-transformed fibroblasts did not show alterations of the basal level of inositol polyphosphates, polyphosphoinositides, diacylglycerol or phosphatidic acid. This indicates that the activity of C-type phospholipases, inositol lipid kinases and diacylglycerol kinase is not altered in dbl-induced transformation. However, dbl-transformed NIH3T3 cells exhibited increased inositol lipid turnover in response to bradykinin. Further analysis revealed significantly higher number of bradykinin receptors in dbl transfectants as compared to control NIH3T3. When several clonally-derived dbl NIH3T3 transfectants were analyzed, we observed a large variation of their bradykinin receptor number. Cell lines exhibiting increased bradykinin binding, however, failed to show augmented mitogenic response to the peptide agonist. Among other oncogenes, only ras showed a similar effect. We conclude that increased bradykinin receptor number is a phenomenon observed with several cell lines transformed by different oncogenes, and it does not correlate with either enhanced mitogenic responsiveness of transformed cells to the peptide, or with the presence of a specific oncogene in the transformant.
我们已检测了由dbl癌基因转化的小鼠成纤维细胞（NIH3T3）与正常细胞相比的多磷酸肌醇代谢情况。dbl转化的成纤维细胞在肌醇多磷酸、多磷酸肌醇、二酰基甘油或磷脂酸的基础水平上未显示出改变。这表明在dbl诱导的转化过程中，C型磷脂酶、肌醇脂质激酶和二酰基甘油激酶的活性未发生改变。然而，dbl转化的NIH3T3细胞对缓激肽的反应表现出肌醇脂质代谢增加。进一步分析显示，与对照NIH3T3相比，dbl转染细胞中的缓激肽受体数量显著更高。当分析多个克隆来源的dbl NIH3T3转染细胞时，我们观察到它们的缓激肽受体数量存在很大差异。然而，表现出缓激肽结合增加的细胞系对该肽激动剂并未显示出增强的促有丝分裂反应。在其他癌基因中，只有ras显示出类似的效应。我们得出结论，缓激肽受体数量增加是几种由不同癌基因转化的细胞系中观察到的一种现象，它与转化细胞对该肽的促有丝分裂反应增强或与转化体中特定癌基因的存在均无关联。
