Falco J P, Taylor W G, Di Fiore P P, Weissman B E, Aaronson S A
Laboratory of Cellular and Molecular Biology, National Cancer Institute, Bethesda, Maryland 20892.
Oncogene. 1988 Jun;2(6):573-8.
Balb/MK epidermal keratinocytes require epidermal growth factor (EGF) for growth in serum-containing medium and terminally differentiate in response to high Ca++ concentration. Several oncogenic retroviruses have been shown to relieve the EGF requirement and to block calcium-induced terminal differentiation. We developed a chemically defined medium to investigate the minimum growth factor requirements for Balb/MK cells, as well as how such requirements might be altered by retroviral oncogenes. In this medium insulin, apparently acting as IGF-1, and EGF supported cell growth in a manner comparable to serum and EGF. Acidic as well as basic fibroblast growth factor (FGF) substituted for EGF but not insulin in supporting Balb/MK proliferation. Infection with retroviruses containing v-ras oncogenes (v-H-ras, v-Ki-ras), oncogenes derived from growth factor receptors (v-erbB, v-fms) or the v-mos oncogene permitted growth in defined medium containing insulin but lacking EGF. The v-fgr oncogene, a member of the src subfamily, was unique in conferring independence from both insulin and EGF. Our findings establish the applicability of this system for biologic assay of epithelial cell growth factors as well as identification of specific growth factor requirements that can be altered or complemented by the actions of specific oncogenes.
Balb/MK表皮角质形成细胞在含血清培养基中生长需要表皮生长因子（EGF），并在高钙离子浓度下终末分化。已显示几种致癌逆转录病毒可解除对EGF的需求并阻断钙诱导的终末分化。我们开发了一种化学成分明确的培养基，以研究Balb/MK细胞的最低生长因子需求，以及这些需求如何可能被逆转录病毒癌基因改变。在这种培养基中，胰岛素显然作为IGF-1发挥作用，并且EGF以与血清和EGF相当的方式支持细胞生长。酸性和碱性成纤维细胞生长因子（FGF）在支持Balb/MK增殖方面可替代EGF但不能替代胰岛素。用含有v-ras癌基因（v-H-ras、v-Ki-ras）、源自生长因子受体的癌基因（v-erbB、v-fms）或v-mos癌基因的逆转录病毒感染，可使细胞在含有胰岛素但缺乏EGF的限定培养基中生长。v-fgr癌基因是src亚家族的成员，其独特之处在于赋予细胞对胰岛素和EGF的独立性。我们的发现确立了该系统在上皮细胞生长因子生物学测定以及鉴定可被特定癌基因的作用改变或补充的特定生长因子需求方面的适用性。
