Expression of protooncogenes c-fos and c-myc in healing of gastric mucosal stress ulcers.
Expression of protooncogenes c-fos and c-myc in healing of gastric mucosal stress ulcers.
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原癌基因c-fos和c-myc在胃粘膜应激性溃疡愈合中的表达。
DOI：
10.1152/ajpgi.1994.266.5.g878
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发表时间：
1994
期刊：
影响因子：
--
通讯作者：
Johnson,LR
中科院分区：
文献类型：
--
作者：
Wang,JY;Johnson,LR
目前的研究确定了这样的假设：原癌基因 c-fos 和 c-myc 的表达参与多胺刺激胃粘膜应激性溃疡愈合的机制。大鼠禁食22 h，置于束缚笼中，水中浸至剑突2-6 h。应激后立即处死动物，或在应激 6 小时后每隔 2 小时至 24 小时处死动物。 2小时后，压力导致泌酸腺粘膜出现可见损伤并诱导鸟氨酸脱羧酶（ODC）活性。 ODC 活性的增加与粘膜多胺腐胺、亚精胺和精胺的增加同时发生。暴露于应激导致 2 小时胃泌酸腺粘膜中出现 c-fos mRNA 和癌蛋白，并在 4 小时消失。 c-myc 的基线表达在应激 6 小时后显着增强，并在 4 小时内保持升高。 c-fos和c-myc mRNA和癌蛋白表达的这种变化先于[3H]胸苷掺入粘膜DNA的速率增加。 α-二氟甲基鸟氨酸（DFMO，500 mg/kg ip）的施用完全阻止了 ODC 活性和多胺水平的显着增加。 DFMO还完全抑制应激大鼠胃粘膜中c-fos的表达并显着降低c-myc mRNA和癌蛋白。愈合过程在 12 小时内显着，但被 DFMO 显着抑制。这些结果表明，1) 暴露于应激的粘膜在多胺合成增加后表现出 c-fos 和 c-myc 表达增加，2) DFMO 抑制多胺生物合成会降低原癌基因表达和粘膜愈合。
The current study determines the hypothesis that expression of protooncogenes c-fos and c-myc is involved in the mechanism of polyamine-stimulated healing in gastric mucosal stress ulcers. Rats were fasted 22 h, placed in restraint cages, and immersed in water to the xiphoid process for 2-6 h. Animals were killed either immediately after stress or at 2-h intervals up to 24 h after 6 h of stress. Stress caused both visible lesions and induction of ornithine decarboxylase (ODC) activity in the oxyntic gland mucosa after 2 h. Increased ODC activity was paralleled by increases in the mucosal polyamines putrescine, spermidine, and spermine. Exposure to stress led to appearance of c-fos mRNA and oncoprotein in the gastric oxyntic gland mucosa at 2 h and its disappearance by 4 h. Baseline expression of c-myc was enhanced significantly after 6 h of stress and remained elevated for 4 h. This change in the expression of c-fos and c-myc mRNA and oncoprotein preceded an increased rate of [3H]thymidine incorporation into mucosal DNA. Administration of alpha-difluoromethylornithine (DFMO, 500 mg/kg ip) totally prevented the marked increases in ODC activity and polyamine levels. DFMO also completely inhibited the expression of c-fos and significantly decreased c-myc mRNA and oncoprotein in the gastric mucosa of stressed rats. The healing process, which was significant by 12 h, was markedly inhibited by DFMO. These results show that 1) mucosa exposed to stress exhibits increased expression of c-fos and c-myc following increased polyamine synthesis and 2) inhibition of polyamine biosynthesis by DFMO decreases both protooncogene expression and mucosal healing.