Jaye M, Lyall R M, Mudd R, Schlessinger J, Sarver N
Rorer Biotechnology, Inc., Horsham, PA 19044.
EMBO J. 1988 Apr;7(4):963-9. doi: 10.1002/j.1460-2075.1988.tb02902.x.
Acidic fibroblast growth factor (aFGF), a polypeptide with a mol. wt of approximately 16,000, is a potent mitogen for a variety of cells and shares 55% amino acid sequence identity with basic FGF. The recent isolation of three new oncogenes which share 35-45% amino acid sequence similarity with the FGFs suggests that the coding sequences for the FGFs themselves may be oncogenic under certain circumstances. To test this hypothesis, we cotransfected 3T3 NR6 cells with factors expressing the aFGF coding sequence and the bacterial neomycin gene. The aFGF produced by cotransfected cells was found only in the cellular homogenate and not in medium conditioned by the cells. Cells expressing aFGF grew to 10 times the density of control cells at saturation and were multilayered and disorganized, similar to transformed cells. The cotransfected cells do not grow in soft agar, but show enhanced soft agar growth relative to controls in the presence of added aFGF and heparin. The aFGF-producing cells formed small, non-progressive tumors when injected subcutaneously into nude mice. Our data suggest that expression of aFGF in NR6 cells results in enhanced growth, and that several traits characteristic of the transformed phenotype are partially expressed.
酸性成纤维细胞生长因子（aFGF）是一种分子量约为16,000的多肽，是多种细胞的强效有丝分裂原，与碱性FGF有55%的氨基酸序列同源性。最近分离出的三种新癌基因与FGFs有35 - 45%的氨基酸序列相似性，这表明FGFs自身的编码序列在某些情况下可能具有致癌性。为了验证这一假设，我们将表达aFGF编码序列的因子与细菌新霉素基因共转染到3T3 NR6细胞中。共转染细胞产生的aFGF仅存在于细胞匀浆中，而不存在于细胞条件培养基中。表达aFGF的细胞在饱和时生长至对照细胞密度的10倍，呈多层且无序排列，类似于转化细胞。共转染细胞在软琼脂中不生长，但在添加aFGF和肝素的情况下，相对于对照显示出增强的软琼脂生长能力。产生aFGF的细胞皮下注射到裸鼠体内时形成小的、不进展的肿瘤。我们的数据表明，aFGF在NR6细胞中的表达导致生长增强，并且部分表达了转化表型的几个特征。
