Vennström B, Bravo R
Differentiation Programme, European Molecular Biology Laboratory, Heidelberg, FGR.
Oncogene. 1987;1(3):271-6.
Murine fibroblasts transformed by the myc oncogene have a reduced growth factor dependence for both anchorage-dependent and anchorage-independent proliferation. Here we show that v-myc-transformed Balb/c 3T3 cells require, in addition to insulin, only platelet-derived growth factor (PDGF) or epidermal growth factor (EGF) for anchorage-dependent growth in serum-free media. PDGF, however, cannot efficiently be substituted by EGF for anchorage-independent growth. The results suggest that constitutive v-myc expression reduces cellular growth factor requirements by non-autocrine mechanisms for proliferation in monolayer cultures. In contrast, v-myc-transformed cells require plasma components and growth factors of the 'competence' type for anchorage-independent growth. We also demonstrate that the requirement for PDGF by the myc-transformed cells can be abrogated by v-K-ras, v-src and v-fos but not the v-raf oncogene. The results demonstrate that oncogenes can cooperate in the expression of the transformed phenotype by also drastically reducing cellular growth factor requirements.
由myc癌基因转化的小鼠成纤维细胞在依赖贴壁和不依赖贴壁的增殖过程中对生长因子的依赖性降低。我们在此表明,v-myc转化的Balb/c 3T3细胞在无血清培养基中进行依赖贴壁生长时,除胰岛素外,仅需要血小板衍生生长因子(PDGF)或表皮生长因子(EGF)。然而,对于不依赖贴壁的生长,EGF不能有效地替代PDGF。结果表明,组成型v-myc表达通过非自分泌机制降低了单层培养中细胞增殖对生长因子的需求。相比之下,v-myc转化的细胞在不依赖贴壁生长时需要血浆成分和“能力”型生长因子。我们还证明,myc转化细胞对PDGF的需求可被v-K-ras、v-src和v-fos消除,但不能被v-raf癌基因消除。结果表明,癌基因还可通过大幅降低细胞对生长因子的需求来协同表达转化表型。