Bréant B, Lavergne C, Rosselin G
Unité INSERM 55, Hôpital Saint-Antoine, Paris, France.
Diabetologia. 1990 Oct;33(10):586-92. doi: 10.1007/BF00400201.
The pancreatic cell line beta TC1, established from insulinomas of transgenic mice carrying a hybrid insulin-promoted large T antigen gene, has retained several characteristics of normal cells, including the insulin content and inducibility of insulin secreting by glucose. We show here that the growth of beta TC1 cells is arrested in low serum-concentration medium. Cells exposed for three days to 0.25% fetal calf serum ceased to incorporate [3H]thymidine but were still able to resume the cell division cycle upon addition of serum. In this cell line, we have determined by cytofluorometry the cell cycle kinetic parameters to be of 21 h, 10 h 30 min and 12 h for the G1, S and G2/M phases, respectively. Quiescent beta TC1 cells constitutively expressed the protooncogene c-jun that codes for the transcriptional factor AP1, as well as cdc2, another cell cycle-related gene. A large transient increase in the expression of the c-fos gene was obtained rapidly, 30 min after addition of serum and a similar increase in c-jun expression after one hour. Expression of the cdc2 gene was also enhanced to a lesser extent. The same effects were also observed in the presence of cycloheximide, thus proving that the expression of these three genes is directly stimulated by serum growth factors. Consequently, quiescent beta TC1 cells provide a good model for studying the short- and long-term effects of growth factors on Beta-cell proliferation.
βTC1胰腺细胞系是从携带杂交胰岛素启动子的大T抗原基因的转基因小鼠的胰岛素瘤中建立的，它保留了正常细胞的几个特征，包括胰岛素含量以及葡萄糖诱导胰岛素分泌的能力。我们在此表明，βTC1细胞的生长在低血清浓度培养基中会停滞。暴露于0.25%胎牛血清三天的细胞停止掺入[3H]胸苷，但在添加血清后仍能恢复细胞分裂周期。在该细胞系中，我们通过细胞荧光测定法确定G1、S和G2/M期的细胞周期动力学参数分别为21小时、10小时30分钟和12小时。静止的βTC1细胞组成性地表达编码转录因子AP1的原癌基因c-jun以及另一个细胞周期相关基因cdc2。添加血清30分钟后，c-fos基因的表达迅速出现大幅瞬时增加，1小时后c-jun表达也有类似增加。cdc2基因的表达也有较小程度的增强。在存在环己酰亚胺的情况下也观察到了相同的效果，从而证明这三个基因的表达是由血清生长因子直接刺激的。因此，静止的βTC1细胞为研究生长因子对β细胞增殖的短期和长期影响提供了一个良好的模型。
