Effects of overexpression of ornithine decarboxylase (ODC) on growth control and oncogene-induced cell transformation.
Effects of overexpression of ornithine decarboxylase (ODC) on growth control and oncogene-induced cell transformation.
复制标题
鸟氨酸脱羧酶（ODC）过度表达对生长控制和癌基因诱导的细胞转化的影响。
作者：
H. Hibshoosh;M. Johnson;Weinstein Ib
酶鸟氨酸脱羧酶（ODC）已涉及控制细胞生长，分化和肿瘤促进。为了进一步阐明其确切作用，将鼠ODC cDNA插入逆转录病毒衍生的载体pMV 7中，并使用逆转录病毒样颗粒感染NIH 3 T3和大鼠6（R6）成纤维细胞。获得了稳定表达ODC酶活性增加5-40倍的衍生物。尽管这些高水平的酶活性的细胞保留了正常的形态，并显示在单层培养或琼脂悬浮液中的生长特性没有重大变化。另一方面，表达高水平ODC的R6细胞显示对活化的c-H-ras癌基因的形态转化的敏感性显著增加。这些结果提供了第一个证据表明，ODC可以与激活的癌基因在细胞转化过程中的合作。虽然其机制尚不清楚，但这些发现可能与多阶段致癌过程有关。
The enzyme ornithine decarboxylase (ODC) has been implicated in the control of cell growth, differentiation and tumor promotion. To further elucidate its precise role a murine ODC cDNA was inserted into the retrovirus-derived vector pMV7 and retrovirus-like particles were used to infect NIH3T3 and rat 6(R6) fibroblasts. Derivatives were obtained that stably express a 5-40 fold increase in ODC enzyme activity. Despite these high levels of enzyme activity the cells retained a normal morphology and displayed no major changes in growth properties in monolayer culture or in agar suspension. On the other hand, R6 cells that expressed high levels of ODC displayed a marked increase in susceptibility to morphologic transformation by an activated c-H-ras oncogene. These results provide the first evidence that ODC can cooperate with an activated oncogene in the process of cell transformation. Although the mechanism is not known, these findings may be relevant to the multistage carcinogenic process.