Haddox M K, Magun B E, Russell D H
Cancer Res. 1980 Mar;40(3):604-8.
Ornithine decarboxylase (ODC) induction during G1 phase of the cell cycle was compared in Rat-1 fibroblasts and in Rat-1 fibroblasts transformed by the B77 wild-type Rous sarcoma virus (RSV) and by the thermosensitive mutant LA24/RSV. In Rat-1 cells, maximal enzyme activity detectable at mid G1 declined to basal levels by G1-S. The ODC increase was inhibited by actinomycin D and cycloheximide and was dependent on the addition of serum growth factors. Rat-1 (B77 wild-type RSV) cells expressed a greater amount of enzyme activity after serum stimulation, and the maximal level of enzyme activity detectable at mid G1 declined only 50% so that elevated ODC was maintained during G1-S transition. The enzyme increase in the transformed cell line was not dependent on serum growth factors. Fresh medium addition alone induced enzyme activity. Induction in the presence or absence of serum required both RNA and protein synthesis. ODC induction in the transformed cells was less sensitive to repression by exogenous putrescine addition. A 100-fold greater concentration of the diamine was required to produce comparable inhibition in the Rat-1 (B77 wild-type RSV) as compared to the Rat-1 cell. These alterations in the characteristics of ODC expression were found to be a consequence of the transforming function of RSV in the Rat-1 cell line transformed by the thermosensitive viral mutant LA24. In response to serum stimulation at the nonpermissive temperature (39 degrees), Rat-1 (thermosensitive mutant LA24/RSV) cells displayed a discrete G1-phase ODC induction while those cells maintained at the permissive temperature (35 degrees) exhibited a greater and prolonged ODC induction in G1 and S phases. A shift from 39 to 35 degrees in the absence of any medium or serum addition stimulated the induction of ODC expressed in a transformed phenotypic manner. Greater concentrations of exogenous putrescine were required to repress the induction of ODC at 35 than at 39 degrees. Alterations in ODC regulation, therefore, may be inherent to the neoplastic phenotypic change.
在细胞周期的G1期，对大鼠1成纤维细胞、由B77野生型劳氏肉瘤病毒（RSV）转化的大鼠1成纤维细胞以及由温度敏感突变体LA24/RSV转化的大鼠1成纤维细胞中的鸟氨酸脱羧酶（ODC）诱导情况进行了比较。在大鼠1细胞中，在G1中期可检测到的最大酶活性在G1-S期降至基础水平。ODC的增加受到放线菌素D和环己酰亚胺的抑制，并且依赖于血清生长因子的添加。大鼠1（B77野生型RSV）细胞在血清刺激后表达出更高水平的酶活性，在G1中期可检测到的最大酶活性水平仅下降了50%，因此在G1-S转换期间ODC水平保持升高。转化细胞系中酶的增加不依赖于血清生长因子。仅添加新鲜培养基就能诱导酶活性。无论有无血清，诱导都需要RNA和蛋白质合成。转化细胞中ODC的诱导对外源腐胺添加的抑制不太敏感。与大鼠1细胞相比，需要高100倍浓度的二胺才能在大鼠1（B77野生型RSV）细胞中产生类似的抑制作用。发现ODC表达特征的这些改变是RSV在由温度敏感病毒突变体LA24转化的大鼠1细胞系中的转化功能的结果。在非允许温度（39摄氏度）下对血清刺激作出反应时，大鼠1（温度敏感突变体LA24/RSV）细胞表现出离散的G1期ODC诱导，而维持在允许温度（35摄氏度）的那些细胞在G1期和S期表现出更大且持续时间更长的ODC诱导。在不添加任何培养基或血清的情况下从39摄氏度转变为35摄氏度会刺激以转化表型方式表达的ODC的诱导。在35摄氏度下比在39摄氏度下需要更高浓度的外源腐胺来抑制ODC的诱导。因此，ODC调节的改变可能是肿瘤表型变化所固有的。
