Fisher P B, Weinstein I B
Cancer Lett. 1980 Jul;10(1):7-17. doi: 10.1016/0304-3835(80)90059-2.
We have compared the effect of extracellular Ca2+ concentration and of phorbol ester tumor promoters on the growth of normal rat liver epithelial cells, a chemically transformed derivative of these cells and a mutant of the latter cells that is temperature sensitive in the expression of transformation. The normal K16 or K22 cells grew considerably better in 1.25 mM Ca2+ than in 0.01 mM Ca2+, whereas their transformed counterpart, W8, grew equally well in 1.25 and 0.01 mM Ca2+. The temperature-sensitive mutant TS 223 exhibited an intermediate phenotype. When grown at either 36 degrees C or 39.5 degrees C, these cells were less Ca2+ dependent than K16 or K22 cells; but they were more Ca2+ dependent than W8 cells. The phorbol ester tumor promoters TPA (12-O-tetradecanoyl-phorbol-13-acetate), PDD (phorbol-12, 13-didecanoate) and PDB (phorbol-12,13-dibenzoate) enhanced the growth of K16 or K22 cells in 0.01 mM Ca2+. On the other hand, the same agents markedly inhibited the growth of W8 and TS 223 cells, at 36 degrees C and 39.5 degrees C, in both low (0.01 mM0 and normal (1.25 mM) Ca2+ concentrations. Two structurally related diterpenes which lack tumor promoting activity on mouse skin, phorbol and 4 alpha PDD, did not alter the growth properties of any of these cell lines, at either low or normal Ca2+ concentrations. Our results indicate, therefore, differences in the responses between normal and transformed rat liver epithelial cells to growth control by extracellular Ca2+ and tumor promoters.
我们比较了细胞外钙离子浓度和佛波酯肿瘤促进剂对正常大鼠肝上皮细胞、这些细胞的化学转化衍生物以及后者细胞的一个在转化表达上对温度敏感的突变体生长的影响。正常的K16或K22细胞在1.25 mM钙离子浓度下比在0.01 mM钙离子浓度下生长得好得多，而它们的转化对应物W8在1.25 mM和0.01 mM钙离子浓度下生长情况相同。温度敏感突变体TS 223表现出中间表型。当在36℃或39.5℃下生长时，这些细胞比K16或K22细胞对钙离子的依赖性小；但它们比W8细胞对钙离子的依赖性大。佛波酯肿瘤促进剂TPA（12 - O - 十四烷酰佛波醇 - 13 - 乙酸酯）、PDD（佛波醇 - 12,13 - 二癸酸酯）和PDB（佛波醇 - 12,13 - 二苯甲酸酯）在0.01 mM钙离子浓度下增强了K16或K22细胞的生长。另一方面，相同的试剂在36℃和39.5℃下，在低（0.01 mM）和正常（1.25 mM）钙离子浓度下均显著抑制W8和TS 223细胞的生长。两种在小鼠皮肤上缺乏肿瘤促进活性的结构相关二萜类化合物，佛波醇和4α - PDD，在低或正常钙离子浓度下均未改变任何这些细胞系的生长特性。因此，我们的结果表明，正常和转化的大鼠肝上皮细胞在对细胞外钙离子和肿瘤促进剂的生长控制反应上存在差异。
