Rodland K D, Jue S F, Magun B E
J Biol Chem. 1986 Apr 15;261(11):5029-33.
The mouse genome contains a retrovirus-like sequence, designated VL30, which is expressed at high levels in transformed cells and which can be induced by exogenously supplied epidermal growth factor (EGF). Binding of EGF to the EGF receptor produces changes in intracellular calcium levels and phospholipase activity which indirectly lead to activation of protein kinase C. We treated AKR-2B cells, Swiss 3T3 cells, and the 3T3 variants NR6 (EGF receptorless) and TNR9 (phorbol ester nonresponsive) with various phorbol ester tumor promoters and with the synthetic diacylglycerol sn-1,2-dioctanoylglycerol. Tumor-promoting phorbol esters (e.g. 12-O-tetradecanoyl phorbol acetate (TPA] increased the level of VL30 expression. Stimulation with either TPA or EGF produced a similar time course of VL30 expression. TPA induced VL30 expression in the EGF-receptorless NR6 cell line, indicating that neither EGF ligand-receptor binding nor phosphorylation of the EGF receptor was required for induction of VL30 expression. Protein synthesis was not required for the TPA-mediated increase in VL30 expression, as pretreatment with cycloheximide did not block or reduce the TPA effect. VL30 expression was also stimulated by treatment with sn-1,2-dioctanoylglycerol, an analog of a probable endogenous activator of protein kinase C. These results suggest that activation of protein kinase C plays a direct role in regulating VL30 expression.
小鼠基因组包含一个类似逆转录病毒的序列，命名为VL30，它在转化细胞中高水平表达，并且可被外源提供的表皮生长因子（EGF）诱导。EGF与EGF受体结合会引起细胞内钙水平和磷脂酶活性的变化，这间接导致蛋白激酶C的激活。我们用各种佛波酯肿瘤启动子以及合成二酰甘油sn-1,2-二辛酰甘油处理AKR-2B细胞、瑞士3T3细胞以及3T3变体NR6（无EGF受体）和TNR9（对佛波酯无反应）。促肿瘤佛波酯（如12-O-十四酰佛波醇乙酸酯（TPA））增加了VL30的表达水平。用TPA或EGF刺激产生了相似的VL30表达时间进程。TPA在无EGF受体的NR6细胞系中诱导了VL30表达，这表明诱导VL30表达既不需要EGF配体-受体结合，也不需要EGF受体的磷酸化。TPA介导的VL30表达增加不需要蛋白质合成，因为用放线菌酮预处理并未阻断或降低TPA的作用。用sn-1,2-二辛酰甘油（一种可能是蛋白激酶C内源性激活剂的类似物）处理也刺激了VL30表达。这些结果表明蛋白激酶C的激活在调节VL30表达中起直接作用。
