Einat M, Resnitzky D, Kimchi A
Proc Natl Acad Sci U S A. 1985 Nov;82(22):7608-12. doi: 10.1073/pnas.82.22.7608.
The G0/G1 to S transition in quiescent BALB/c 3T3 cells stimulated by serum growth factors can be specifically blocked by the administration of interferon (IFN) to the system. In the present communication, we studied whether IFN inhibits the early events in the G0/G1 phase that are initiated by the platelet-derived growth factor (PDGF). The results show that IFN inhibits most of the PDGF-mediated increase of c-myc, ornithine decarboxylase, and beta-actin mRNAs measured 3 hr after stimulation. c-fos mRNA levels are reduced by IFN as early as 20 min after exposure of the quiescent cells to PDGF. The expression of several genes that belong to the competence gene family is, therefore, inhibited by IFN and this could account for the failure of the IFN-treated cells to enter into the S phase when growth factors present in the platelet-poor plasma are added. We also report that the PDGF-mediated increase in the uptake of deoxyglucose is not impaired by IFN, thus suggesting that the early effects of IFN on gene expression do not result from inhibition of binding of PDGF to its cell-surface receptors. Unlike the direct stimulatory effect of PDGF, which is not sensitive to cycloheximide, the inhibitory effect of IFN on c-myc mRNA levels depends in part on protein synthesis. We propose that a putative product of one of the IFN-induced genes could mediate the decrease in expression of the PDGF-regulated gene family.
血清生长因子刺激静止的BALB/c 3T3细胞从G0/G1期向S期转变时，向该系统中加入干扰素（IFN）可特异性阻断这一过程。在本通讯中，我们研究了IFN是否抑制由血小板衍生生长因子（PDGF）引发的G0/G1期早期事件。结果表明，IFN抑制了刺激3小时后检测到的大部分由PDGF介导的c-myc、鸟氨酸脱羧酶和β-肌动蛋白mRNA的增加。静止细胞暴露于PDGF后最早在20分钟时，IFN就使c-fos mRNA水平降低。因此，IFN抑制了几个属于感受态基因家族的基因的表达，这可以解释当加入血小板贫浆中存在的生长因子时，经IFN处理的细胞无法进入S期的原因。我们还报告说，IFN不会损害PDGF介导的脱氧葡萄糖摄取增加，因此表明IFN对基因表达的早期影响并非源于抑制PDGF与其细胞表面受体的结合。与对放线菌酮不敏感的PDGF的直接刺激作用不同，IFN对c-myc mRNA水平的抑制作用部分取决于蛋白质合成。我们提出，IFN诱导基因之一的假定产物可能介导PDGF调节基因家族表达的降低。
