ONCOGENE EXPRESSION DURING CELL DIFFERENTIATION AND DEVELOPMENT

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The ets gene expression (ets-1, ets-2 and erg) was examined in fetal thymocytes from different stages of development in isolated subsets of adult thymocytes and in peripheral T-lymphocytes. The ets-1 gene expression was first detected at day 18 in fetal thymocytes, corresponding to the first appearance of CD4-positive (CD4-positive, CD8-negative) thymocytes, and reaches maximal/plateau levels of expression in the thymus at 1-2 days after birth. The ets-2 gene expression is detected at least one day earlier, coinciding with the presence of both double-positive (CD4-positive, CD8-positive) and double-negative (CD4-negative, CD8-negative) blast thymocytes and reaches maximal/plateau levels one day before birth. In the adult thymus, ets-1 and ets-2 mRNA expression is ten- to eight-fold higher, respectively, in the CD4-positive subset than in the other subsets examined. Higher levels of p55 ets-1 protein were also shown to exist in the CD4-positive subset. Both the CD4- positive and the CD8-positive T cell subsets had lower ets RNA levels than the CD4-positive thymocytes. These results suggest that ets-2 and, more particularly, ets-1 gene products play an important role in T-cell development and differentiation and are not simply associated with proliferating cells, which are observed at a higher frequency in fetal thymocytes, or dull Ly-1 (low CD5- positive) and double-negative adult thymocytes. The ets-1 and ets- 2 mRNA level did not change during erythroid differentiation. The role of ets gene products in maturation of helper function and in T-cell activation and differentiation are under investigation. The ets gene expression will also be studied in specific thymocyte and T-cell subsets derived from tumor tissues.