Hajitou A, Baramova E N, Bajou K, Noë V, Bruyneel E, Mareel M, Collette J, Foidart J M, Calberg-Bacq C M
Laboratory of Fundamental Virology and Immunology, Institute of Pathology, University of Liège, Belgium.
Oncogene. 1998 Oct 22;17(16):2059-71. doi: 10.1038/sj.onc.1202126.
Fibroblast Growth Factors 3 (FGF-3) and 4 (FGF-4) were compared for the effects they each exert on EF43 mouse cells. This non-transformed mammary cell line appears to be myoepithelial mainly because it expresses alpha-smooth muscle actin. The EF43 cells were infected with similar vectors that carry either the short fgf-3 sequence (the product of which goes into the secretory pathway), fgf-4 or the selection gene only as control. In syngeneic animals, EF43.fgf-3 cells were tumorigenic only when orthotopically implanted whereas EF43.fgf-4 cells invariably gave rise to aggressive tumors. However, both tumor types were metastatic as evidenced by the blue micrometastases observed when the implanted cells expressed lacZ. In vitro, the FGF-3 producing cells were strongly invasive in matrigel coated chambers whereas the EF43.fgf-4 cells only were invasive in type I-collagen gels. Interestingly, FGF-3 production greatly stimulated the synthesis of pro-MMP-9 (Matrix Metalloprotease-9) and, to a lesser extent, that of pro-MMP-2. FGF-3 also up-regulated the production of plasminogen activators. In contrast, FGF-4 had no effect on these secretions and the medium conditioned by the EF43.fgf-4 cells displayed the largest plasminogen activator-inhibitor activity. These results show that FGF-3 and FGF-4 have distinct mechanisms of action on myoepithelial cells.
对成纤维细胞生长因子3（FGF - 3）和成纤维细胞生长因子4（FGF - 4）对EF43小鼠细胞各自产生的影响进行了比较。这种未转化的乳腺细胞系似乎主要是肌上皮细胞，因为它表达α - 平滑肌肌动蛋白。用携带短fgf - 3序列（其产物进入分泌途径）、fgf - 4或仅作为对照的选择基因的相似载体感染EF43细胞。在同基因动物中，EF43.fgf - 3细胞仅在原位植入时具有致瘤性，而EF43.fgf - 4细胞总是引发侵袭性肿瘤。然而，两种肿瘤类型都有转移，这可通过植入细胞表达lacZ时观察到的蓝色微转移来证明。在体外，产生FGF - 3的细胞在基质胶包被的小室中具有强烈的侵袭性，而EF43.fgf - 4细胞仅在I型胶原凝胶中具有侵袭性。有趣的是，FGF - 3的产生极大地刺激了前基质金属蛋白酶 - 9（基质金属蛋白酶 - 9）的合成，在较小程度上也刺激了前基质金属蛋白酶 - 2的合成。FGF - 3还上调了纤溶酶原激活剂的产生。相反，FGF - 4对这些分泌没有影响，并且由EF43.fgf - 4细胞条件培养基显示出最大的纤溶酶原激活剂抑制活性。这些结果表明FGF - 3和FGF - 4对肌上皮细胞具有不同的作用机制。
