Moscatelli D, Quarto N
Department of Cell Biology, New York University Medical Center, New York.
J Cell Biol. 1989 Nov;109(5):2519-27. doi: 10.1083/jcb.109.5.2519.
When NIH 3T3 cells were transfected with the cDNA for basic fibroblast growth factor (bFGF), most cells displayed a transformed phenotype. Acquisition of a transformed phenotype was correlated with the expression of high levels of bFGF (Quarto et al., 1989). Cells that had been transformed as a result of transfection with bFGF cDNA had a decreased capacity to bind 125I-bFGF to high affinity receptors. NIH 3T3 cells transfected with bFGF cDNA that expressed lower levels of bFGF were not transformed and had a normal number of bFGF receptors. NIH 3T3 cells transfected with the hst/Kfgf oncogene, which encodes a secreted molecule with 45% homology to bFGF, also displayed a transformed phenotype and decreased numbers of bFGF receptors. However, NIH 3T3 cells transfected with the H-ras oncogene were transformed but had a normal number of bFGF receptors. Thus, transformation by bFGF-like molecules resulted in downregulation of bFGF receptors. Receptor number was not affected by cell density for both parental NIH 3T3 cells and transformed cells. In the cells transfected with bFGF cDNA that were not transformed, the receptors could be downregulated in response to exogenous bFGF. Conditioned medium from transformed transfected cells contained sufficient quantities of bFGF to downregulate bFGF receptors on parental NIH 3T3 cells. Thus, the downregulation of bFGF receptors seemed related to the presence of bFGF in an extracytoplasmic compartment. Treatment of the transformed transfected NIH 3T3 cells with suramin, which blocks the interaction of bFGF with its receptor, reversed the morphological transformation and restored receptors almost to normal numbers. These results demonstrate that in these cells bFGF transforms cells by interacting with its receptor and that bFGF and hst/K-fgf may use the same receptor.
当用碱性成纤维细胞生长因子（bFGF）的cDNA转染NIH 3T3细胞时，大多数细胞呈现出转化表型。获得转化表型与高水平bFGF的表达相关（夸尔托等人，1989年）。因用bFGF cDNA转染而转化的细胞与125I-bFGF结合到高亲和力受体的能力下降。用表达较低水平bFGF的bFGF cDNA转染的NIH 3T3细胞未发生转化，且bFGF受体数量正常。用hst/Kfgf癌基因转染的NIH 3T3细胞，该基因编码一种与bFGF有45%同源性的分泌分子，也呈现出转化表型且bFGF受体数量减少。然而，用H-ras癌基因转染的NIH 3T3细胞发生了转化，但bFGF受体数量正常。因此，bFGF样分子介导的转化导致bFGF受体下调。亲本NIH 3T3细胞和转化细胞的受体数量均不受细胞密度影响。在未发生转化的用bFGF cDNA转染的细胞中，受体可因外源性bFGF而下调。来自转化转染细胞的条件培养基含有足够量的bFGF，可下调亲本NIH 3T3细胞上的bFGF受体。因此，bFGF受体的下调似乎与细胞外区域中bFGF的存在有关。用苏拉明处理转化转染的NIH 3T3细胞，苏拉明可阻断bFGF与其受体的相互作用，逆转了形态转化并使受体数量几乎恢复正常。这些结果表明，在这些细胞中bFGF通过与其受体相互作用来转化细胞，并且bFGF和hst/K-fgf可能使用相同的受体。
