ORNITHINE DECARBOXYLASE ACTIVITY IS CRITICAL FOR CELL-TRANSFORMATION
ORNITHINE DECARBOXYLASE ACTIVITY IS CRITICAL FOR CELL-TRANSFORMATION
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DOI：
10.1038/360355a0
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发表时间：
1992-11-26
期刊：
影响因子：
64.8
通讯作者：
HOLTTA, E
中科院分区：
文献类型：
--
作者：
AUVINEN, M;PAASINEN, A;HOLTTA, E
鸟氨酸脱羧酶是多胺合成的关键调节因子 1-3，而多胺对于细胞增殖至关重要 4,5。该酶的表达在生长因子 1-3 刺激下短暂增加，但在致癌物 6,7、病毒 8-10 或癌基因 11-14 诱导的细胞转化过程中被组成型激活。为了测试鸟氨酸脱羧酶是否可能是转化和致癌本身的常见介质，我们用携带有义和反义方向编码人鸟氨酸脱羧酶的互补DNA的表达载体转染NIH3T3细胞。该酶表达的增加（内源水平的 50-100 倍）不仅诱导细胞转化，而且还诱导软琼脂中不依赖贴壁的生长，并增加 M(r) 130K 蛋白的酪氨酸磷酸化。鸟氨酸脱羧酶反义RNA的表达与上皮样形态和细胞增殖减少相关。此外，使用特异性抑制剂阻断内源酶或合成反义RNA可防止温度敏感的v-src癌基因对大鼠成纤维细胞的转化。我们的结果表明编码鸟氨酸脱羧酶的基因是调节细胞生长和转化的中心原癌基因。
THE enzyme ornithine decarboxylase is the key regulator of the synthesis of polyamines1-3 which are essential for cell proliferation4,5. Expression of this enzyme is transiently increased upon stimulation by growth factors1-3, but becomes constitutively activated during cell transformation induced by carcinogens6,7, viruses8-10 or oncogenes11-14. To test whether ornithine decarboxylase could be a common mediator of transformation and oncogenic itself, we transfected NIH3T3 cells with expression vectors carrying the complementary DNA encoding human ornithine decarboxylase in sense and antisense orientations. The increased expression of the enzyme (50-100-times endogenous levels) induced not only cell transformation, but also anchorage-independent growth in soft agar and increased tyrosine phosphorylation of a protein of M(r) 130K. Expression of ornithine decarboxylase antisense RNA was associated with an epithelioid morphology and reduced cell proliferation. Moreover, blocking the endogenous enzyme using specific inhibitor or synthesizing antisense RNA prevented transformation of rat fibroblasts by temperature-sensitive v-src oncogene. Our results imply that the gene encoding ornithine decarboxylase is a proto-oncogene central for regulation of cell growth and transformation.