Analysis of c-ets gene expression during cell proliferation and differentiation indicate that (i) the ets-1 and ets-2 genes are activated by serum addition to quiescent fibroblast cells before DNA synthesis; (ii) the increase in the level of ets mRNAs is due to an increase in the transcription of these genes and stabilization of their mRNA; (iii) during hepatic regeneration, only the ets-2 mRNA, but not the ets-1 mRNA, level increases before DNA synthesis; (iv) the ets-1 and ets-2 genes are differentially regulated; (v) in vivo ets-2 gene expression is regulated mainly at the post-transcriptional level; (vi) addition of TPA to HL60 cells appears to stabilize both ets-1 and ets-2 mRNAs; and (vii) subcellular fractionation indicates that 56 kDa protein is localized in the nucleus, whereas 55 kDa ets-1 protein localized in the cytoplasm and the nucleus. These results suggest that the ets-2 gene products accumulate well before DNA synthesis and its expression is intrinsically linked with cell proliferation and follows a pattern similar to other members of the nuclear oncogene family. Depending on particular cell or tissue type, different control mechanisms may be operative in regulating ets gene loci. The role of ets gene products in T-cell proliferation in different types of T-cells, hematopoietic tumors and in hepatoma are under investigation.
