Rogelj S, Weinberg R A, Fanning P, Klagsbrun M
Whitehead Institute, Cambridge, Massachusetts 02142.
Nature. 1988 Jan 14;331(6152):173-5. doi: 10.1038/331173a0.
Basic fibroblast growth factor (bFGF) is a potent growth and angiogenic factor that is found in abundance in tissues such as brain, hypothalamus, kidney and cartilage. Despite this copious production of bFGF, most of these tissues are not undergoing either active growth or angiogenesis, suggesting that bFGF activity must be regulated so as to prevent autostimulation of cell growth. In cultured cells, bFGF is associated mainly with cells and basement membranes and is not released into the medium. Prevention of release could be a mechanism for regulation of bFGF activity and may be a consequence of the apparent absence of a secretory-signal sequence in the bFGF protein. Here we investigate whether this regulation can be overridden through the forced secretion of bFGF. Such secretion might provide the bFGF access to its receptor and in turn lead to autocrine transformation of the cell. We report that bFGF, as specified by a recombinant plasmid, is itself unable to induce such transformation, but acquires this ability after fusion with a secretory-signal sequence. The resulting transformants undergo unusual morphological alteration and display tumorigenicity.
碱性成纤维细胞生长因子（bFGF）是一种强效的生长和血管生成因子，在脑、下丘脑、肾脏和软骨等组织中大量存在。尽管bFGF大量产生，但这些组织中的大多数既没有进行活跃的生长也没有发生血管生成，这表明bFGF的活性必须受到调节，以防止细胞生长的自我刺激。在培养的细胞中，bFGF主要与细胞和基底膜结合，不会释放到培养基中。防止释放可能是调节bFGF活性的一种机制，并且可能是bFGF蛋白中明显缺乏分泌信号序列的结果。在这里，我们研究这种调节是否可以通过强制分泌bFGF来克服。这种分泌可能使bFGF能够接触到其受体，进而导致细胞的自分泌转化。我们报告说，由重组质粒指定的bFGF本身无法诱导这种转化，但在与分泌信号序列融合后获得了这种能力。产生的转化体经历异常的形态改变并表现出致瘤性。
