Hall S H, Berthelon M C, Avallet O, Saez J M
INSERM U307, Hôpital Debrousse, Lyon, France.
Endocrinology. 1991 Sep;129(3):1243-9. doi: 10.1210/endo-129-3-1243.
The nuclear protooncogenes have been implicated in the coordinate regulation of gene expression during cell proliferation and differentiation. Previous work has shown that LH and human h CG as well as several growth factors including epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), transforming growth factor-beta, and insulin-like growth factor-I play a role in Leydig cell differentiated functions. To evaluate the possibility that protooncogenes mediate long term effects of these factors, their action on the levels of c-fos, c-jun, jun-B, and c-myc messenger (m) RNAs was studied. hCG (10(-9) M) produced a time-dependent increase in c-fos (9-fold), jun-B (18-fold) and c-myc (5-fold) mRNA levels but did not affect c-jun. The concentration of hCG required for half-maximal stimulation (ED50 = 7 +/- 4 x 10(-12) M) was similar to that required to induce half-maximal testosterone production. At optimal concentrations, the effects of EGF and bFGF on c-fos and jun-B mRNAs were lower than those induced by hCG, but their effects on c-myc mRNA were higher. In addition, they stimulated c-jun. Moreover, EGF and bFGF potentiated the effects of hCG on c-fos and jun-B, whereas hCG potentiated the action of growth factors on c-jun. Transforming growth factor-beta increased only jun-B mRNA, whereas insulin-like growth factor I increased c-fos, jun-B, and c-myc but less effectively than hCG. Lastly, the phorbol ester phorbol 12-myristate 13-acetate increased the level of the four protooncogene mRNAs, and its effects on c-fos and c-myc were significantly higher than those produced by hCG. These data indicate that the regulation of protooncogene mRNAs in normal Leydig cells is multifactorial. They also show differential responsiveness of the members of the Jun family to several factors. Our results are consistent with the hypothesis that the Fos and Jun families of regulatory proteins could play a role in mediating long term responses to the complex array of hormones and growth factors to which Leydig cells are exposed in vivo.
核原癌基因与细胞增殖和分化过程中基因表达的协调调控有关。先前的研究表明，促黄体生成素（LH）、人绒毛膜促性腺激素（hCG）以及包括表皮生长因子（EGF）、碱性成纤维细胞生长因子（bFGF）、转化生长因子-β和胰岛素样生长因子-I在内的多种生长因子在睾丸间质细胞的分化功能中发挥作用。为了评估原癌基因介导这些因子长期作用的可能性，研究了它们对c-fos、c-jun、jun-B和c-myc信使核糖核酸（mRNA）水平的影响。hCG（10^(-9) M）使c-fos（9倍）、jun-B（18倍）和c-myc（5倍）的mRNA水平呈时间依赖性增加，但不影响c-jun。半数最大刺激所需的hCG浓度（ED50 = 7 +/- 4 x 10^(-12) M）与诱导半数最大睾酮产生所需的浓度相似。在最佳浓度下，EGF和bFGF对c-fos和jun-B mRNA的影响低于hCG诱导的影响，但它们对c-myc mRNA的影响更高。此外，它们还刺激了c-jun。而且，EGF和bFGF增强了hCG对c-fos和jun-B的作用，而hCG增强了生长因子对c-jun的作用。转化生长因子-β仅增加jun-B mRNA，而胰岛素样生长因子I增加c-fos、jun-B和c-myc，但效果不如hCG。最后，佛波酯十四酰佛波醇乙酯增加了四种原癌基因mRNA的水平，其对c-fos和c-myc的影响明显高于hCG产生的影响。这些数据表明，正常睾丸间质细胞中原癌基因mRNA的调控是多因素的。它们还显示了Jun家族成员对几种因子的不同反应性。我们的结果与以下假设一致，即Fos和Jun家族的调节蛋白可能在介导对睾丸间质细胞在体内所接触的复杂激素和生长因子阵列的长期反应中发挥作用。
