Dong X F, Berthois Y, Dussert C, Isnardon D, Palmari J, Martin P M
Laboratoire de Cancérologie Expérimentale, Faculté Médecine Nord, Marseille, France.
Anticancer Res. 1992 Nov-Dec;12(6B):2085-92.
EGF is known to play a very important role in the growth regulation of tumor cells. We have determined the effect of EGF in the absence and in the presence of serum on the cell cycle of MCF-7 cells synchronized in the G1 phase by serum deprivation. In the presence of 1% serum, EGF was found to increase DNA synthesis to 120% of control (P < 0.02), but did not modify the transition time from G1 into S phases, nor the cell doubling time during the first generation following the cell synchronization. The autoradiography analysis of 3H-thymidine labeled cells indicated that, following 24 h of EGF treatment, a constant additional number of cells (11 +/- 1.5%, P < 0.002) were recruited into the S phase in the presence as well as in the absence of serum. These data indicate that EGF exerts its mitogenic effect on MCF-7 cells by increasing the percent of S phase cells without modulating the cell doubling time. However, in the absence of serum a significant increase of thymidine incorporation in whole cells required 12 h of EGF treatment, whereas a 6 h-incubation with EGF was sufficient to stimulate DNA synthesis when synchronized cells were pretreated with serum for 6 h, suggesting that EGF sensitivity is dependent on the cell advance into the G1 phase at the moment of EGF addition. Topographical analysis of 3H-thymidine-labeled cells aimed at determining the spatial distribution of cells in culture revealed that EGF-stimulated cells were disposed near proliferative cells, indicating the local influence on cell proliferation. Taken together, our results suggest that in the MCF-7 cell line, EGF acts in the G1 phase by increasing the proportion of S cells without affecting the duration of the cell cycle. In our model, EGF seems to act as a "progression factor", in that it stimulates only cells already traversing a certain stage in the G1 phase under the action of serum factors, cell secreted diffusible products and cell-cell contact.
已知表皮生长因子（EGF）在肿瘤细胞的生长调节中发挥着非常重要的作用。我们已经确定了在血清缺乏和存在的情况下，EGF对经血清剥夺同步于G1期的MCF-7细胞的细胞周期的影响。在1%血清存在的情况下，发现EGF可使DNA合成增加至对照的120%（P < 0.02），但并未改变从G1期进入S期的过渡时间，也未改变细胞同步化后第一代细胞的倍增时间。对3H-胸腺嘧啶核苷标记细胞的放射自显影分析表明，在EGF处理24小时后，无论有无血清，恒定数量的额外细胞（11 +/- 1.5%，P < 0.002）被募集进入S期。这些数据表明，EGF通过增加S期细胞的百分比而不对细胞倍增时间进行调节，从而对MCF-7细胞发挥其促有丝分裂作用。然而，在无血清的情况下，全细胞中胸腺嘧啶核苷掺入的显著增加需要EGF处理12小时，而当同步化细胞先用血清预处理6小时时，与EGF孵育6小时就足以刺激DNA合成，这表明EGF敏感性取决于在添加EGF时细胞进入G1期的进程。对3H-胸腺嘧啶核苷标记细胞进行的旨在确定培养物中细胞空间分布的拓扑分析表明，EGF刺激的细胞分布在增殖细胞附近，表明其对细胞增殖具有局部影响。综上所述，我们的结果表明，在MCF-7细胞系中，EGF在G1期起作用，通过增加S期细胞的比例而不影响细胞周期的持续时间。在我们的模型中，EGF似乎作为一种“进展因子”起作用，因为它仅刺激在血清因子、细胞分泌的可扩散产物和细胞-细胞接触的作用下已经穿越G1期某个阶段的细胞。
