Restoration of several morphological characteristics of normal fibroblasts in sarcoma cells treated with adenosine-3':5'-cyclic monphosphate and its derivatives.

Restoration of several morphological characteristics of normal fibroblasts in sarcoma cells treated with adenosine-3':5'-cyclic monphosphate and its derivatives.
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用腺苷-3:5-环单磷酸及其衍生物处理的肉瘤细胞中正常成纤维细胞的几种形态特征的恢复。

DOI:
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发表时间:
1971
影响因子:
11.1
通讯作者:
I. Pastan
I. Pastan
中科院分区:
综合性期刊1区
文献类型:
--
作者:
G. S. Johnson;R. Friedman;I. Pastan

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在组织培养中生长的肉瘤细胞具有不同于正常成纤维细胞的形态和生长特征。当细胞与二丁酰-环AMP或丁酰-环AMP(0.1-1 mM)或环AMP(3 mM)加茶碱(1 mM)孵育,但不与ATP、ADP、AMP、腺嘌呤或腺苷(1-7 mM)孵育时,正常成纤维细胞的几种形态学特征得以恢复。细胞体变长,形成明显的狭窄突起。随着孵育时间的延长,细胞显示出较少的堆积或变成多边形的倾向。此外,L-929和Rous肉瘤转化的仓鼠细胞以接触抑制特征的平行阵列定向。只要丁酰环AMP存在,细胞就保持其改变的形态,但在其去除后恢复。放线菌酮、嘌呤霉素和放线菌素D的实验表明,反应需要蛋白质合成,而不是RNA合成。微管蛋白可能参与其中。在正常成纤维细胞或各种上皮细胞中未观察到反应。这些数据表明,环AMP可能是一个重要的因素,在正常的成纤维细胞的形态和这种功能的决定可能会丢失或改变在转型。
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.