Loss of epidermal growth factor requirement and malignant transformation.
Loss of epidermal growth factor requirement and malignant transformation.
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表皮生长因子需求丧失和恶变。
DOI：
10.1073/pnas.76.8.3937
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发表时间：
1979
影响因子：
11.1
通讯作者：
A. Pardee
中科院分区：
文献类型：
--
作者：
P. V. Cherington;B. Smith;A. Pardee
在组织培养中，血清提供了调节和限制正常细胞生长的生长因子。被恶性转化的动物细胞在培养中通常表现出对生长所需血清的减少。我们使用了一种明确的、无血清的培养基来确定哪些生长因子对于转化的叙利亚和中国仓鼠成纤维细胞的生长是必不可少的。培养液中的四种生长因子--表皮生长因子(EGF)、胰岛素、成纤维细胞生长因子和转铁蛋白--可以根据需要添加或省略。对EGF需求的减少与化学转化细胞(甲烷磺酸乙酯)在裸鼠体内的致瘤性最密切相关。所有受检品系对转铁蛋白的需求都保持不变，转铁蛋白在整个生长周期中都是必需的，而其他因素主要是在G(1)期所需的。失去了EGF需求但保留了胰岛素需求的品系由于胰岛素缺乏而被阻止在G(1)中，这表明它们的生长控制系统仍然存在。用甲烷磺酸乙酯进行诱变也可以产生转化细胞对血清中未知因素的要求。我们得出结论，在培养和肿瘤发生中，降低血清需求的第一步是放松EGF的生长调节功能。
Serum provides growth factors that regulate and limit the growth of normal cells in tissue culture. Animal cells that are malignantly transformed usually exhibit diminished serum requirements for growth in culture. We have used a defined, serum-free medium to determine which of these growth factors becomes dispensable for the growth of transformed Syrian and Chinese hamster fibroblast cells. The medium's four growth factors-epidermal growth factor (EGF), insulin, fibroblast growth factor, and transferrin-were added or omitted as desired. A decreased requirement for EGF was most closely related to tumorigenicity of chemically (ethyl methanesulfonate) transformed cells in nude mice. All lines examined retained their requirement for transferrin, which is needed throughout the growth cycle, in contrast to the other factors, which are needed primarily in G(1) phase. Lines that had lost their EGF requirement but had retained their insulin requirement were arrested in G(1) by insulin deficiency, indicating that their growth control system remained. Mutagenesis with ethyl methanesulfonate can also create requirements of the transformed cells for unknown factors in serum. We conclude that an initial step that reduces the serum requirement in culture, and in tumorigenesis, is relaxation of the growth-regulatory function of EGF.