TIS gene expression in cultured rat astrocytes: induction by mitogens and stellation agents

The expression of a number of TIS genes (Lim et al.: Oncogene 1:263-270, 1987) was examined in secondary cultures of rat neocortical astrocytes treated with mitogens and stellation agents, to study the early nuclear events which accompany the induction of glial proliferation and/or differentiation. Tetradecanoyl phorbol acetate (TPA), epidermal growth factor, and fibroblast growth factor, three mitogens for astrocytes, stimulated marked, rapid, and transient increases in TIS gene mRNAS. TIS10, which is not expressed in rat PC12 pheochromocytoma cells, could be induced by these mitogens in rat astrocytes. Dibutyryl cyclic adenosine monophosphate and forskolin, which induce rapid stellation in astrocytes, and ganglioside GM1, a potent mitogen as well as an antagonist of the induction and maintenance of stellation, all induced TIS gene expression. Thus, a broad range of agents which elicit both proliferative and differentiation responses in astrocytes are capable of inducing a family of genes that may play a role in the early events of signal transduction.