Yamasaki H, Katoh F
International Agency for Research on Cancer, Lyon, France.
Cancer Res. 1988 Jun 15;48(12):3490-5.
In order to investigate further the role of gap-junctional intercellular communication in the process of cell transformation, we examined the effects of chemicals that modulate gap-junctional communication on the induction and maintenance of transformed foci in BALB/c 3T3 cells. When dibutyryl cyclic AMP, retinoic acid, fluocinolone acetonide, or dexamethasone was added during the induction of cell transformation by standard (3-methylcholanthrene alone) or two-stage (low dose of 3-methylcholanthrene plus phorbol ester) protocols, there was a significant decrease in the number of transformed foci. When BALB/c 3T3 cells are transformed, there is selective intercellular communication between transformed and between surrounding nontransformed cells: transformed cells communicate among themselves but not with surrounding normal cells. Addition of dibutyryl cyclic AMP, retinoic acid, fluocinolone acetonide, or dexamethasone to culture dishes in which transformed foci were present induced communication between transformed cells and surrounding normal cells. In the continuous presence of these chemicals, there was a clear decrease in the number of transformed foci. These chemicals therefore appear capable of reestablishing intercellular communication between transformed and nontransformed cells and of diminishing the number of transformed foci. However, when transformed cells were isolated and placed in culture dishes at clonal density in the presence of these chemicals, there was hardly any decrease in the number of transformed colonies, suggesting that the chemicals cannot revert the phenotype of transformed cells in the absence of normal cells. These results suggest that chemicals that modulate intercellular communication not only inhibit the induction of transformed foci but also revert transformed cells to the normal phenotypes by establishing intercellular communication with surrounding normal cells.
为了进一步研究间隙连接细胞间通讯在细胞转化过程中的作用，我们检测了调节间隙连接通讯的化学物质对BALB/c 3T3细胞中转化灶的诱导和维持的影响。当在通过标准方案（单独使用3-甲基胆蒽）或两阶段方案（低剂量3-甲基胆蒽加佛波酯）诱导细胞转化期间添加二丁酰环磷酸腺苷、视黄酸、醋酸氟轻松或地塞米松时，转化灶的数量显著减少。当BALB/c 3T3细胞发生转化时，转化细胞之间以及与周围未转化细胞之间存在选择性细胞间通讯：转化细胞彼此之间通讯，但不与周围正常细胞通讯。向存在转化灶的培养皿中添加二丁酰环磷酸腺苷、视黄酸、醋酸氟轻松或地塞米松可诱导转化细胞与周围正常细胞之间的通讯。在这些化学物质持续存在的情况下，转化灶的数量明显减少。因此，这些化学物质似乎能够重新建立转化细胞与未转化细胞之间的细胞间通讯，并减少转化灶的数量。然而，当将转化细胞分离并以克隆密度置于含有这些化学物质的培养皿中时，转化集落的数量几乎没有减少，这表明在没有正常细胞的情况下，这些化学物质不能使转化细胞的表型恢复正常。这些结果表明，调节细胞间通讯的化学物质不仅抑制转化灶的诱导，还通过与周围正常细胞建立细胞间通讯使转化细胞恢复为正常表型。
