Johnson G S, Friedman R M, Pastan I
Proc Natl Acad Sci U S A. 1971 Feb;68(2):425-9. doi: 10.1073/pnas.68.2.425.
Sarcoma cells growing in tissue culture have morphological and growth characteristics different than normal fibroblasts. Several of the morphological characteristics of normal fibroblasts are regained when the cells are incubated with dibutyryl-cyclic AMP or butyryl-cyclic AMP (0.1-1 mM), or cyclic AMP (3 mM) plus theophylline (1 mM), but not with ATP, ADP, AMP, adenine, or adenosine (1-7 mM). The cell bodies become elongated; distinct narrow processes are formed. With prolonged incubation, the cells show less tendency to pile up or become polygonal. Further, L-929 and Rous sarcomatransformed hamster cells orient in parallel arrays characteristic of contact inhibition. The cells retain their altered morphology as long as the butyryl-cyclic AMP is present, but revert after its removal. Experiments with cycloheximide, puromycin, and actinomycin D indicate that protein Synthesis, but not RNA synthesis, is required for the response. Microtubular proteins may be involved. No response is observed with normal fibroblasts or with various epithelial cells. The data suggest that cyclic AMP may be an important factor in the determination of morphology of normal fibroblasts and this function may be lost or altered during transformation.
在组织培养中生长的肉瘤细胞具有与正常成纤维细胞不同的形态和生长特性。当细胞与二丁酰环磷酸腺苷或丁酰环磷酸腺苷（0.1 - 1 mM），或环磷酸腺苷（3 mM）加茶碱（1 mM）一起孵育时，正常成纤维细胞的一些形态特征得以恢复，但与三磷酸腺苷、二磷酸腺苷、一磷酸腺苷、腺嘌呤或腺苷（1 - 7 mM）一起孵育时则不能恢复。细胞体变得细长；形成明显的狭窄突起。随着孵育时间延长，细胞堆积或变成多边形的趋势减弱。此外，L - 929和劳氏肉瘤转化的仓鼠细胞呈平行排列，具有接触抑制的特征。只要存在丁酰环磷酸腺苷，细胞就保持其改变后的形态，但去除后会恢复。用环己酰亚胺、嘌呤霉素和放线菌素D进行的实验表明，这种反应需要蛋白质合成，但不需要RNA合成。微管蛋白可能参与其中。正常成纤维细胞或各种上皮细胞未观察到反应。数据表明，环磷酸腺苷可能是决定正常成纤维细胞形态的一个重要因素，并且这种功能在转化过程中可能会丧失或改变。
