期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1985
卷号：82
期号：12
页码：4221-4224
DOI：10.1073/pnas.82.12.4221
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Increased expression of the cellular oncogene c-myc has recently been demonstrated in some types of proliferating non-neoplastic cells, including lectin mitogen-stimulated lymphocytes, suggesting a role for this protooncogene in the regulation of growth of normal cells. Here we report the effects of several modulators of lymphocyte proliferation on the steady-state levels of c-myc mRNA in human peripheral blood mononuclear cells (PBMC). Stimulating PBMC with lectin mitogen phytohemagglutinin (PHA), phorbol ester phorbol 12-myristate 13-acetate, calcium ionophore ionomycin, or monoclonal antibody OKT3 (anti-antigen receptor complex) produced marked increases in c-myc mRNA levels within 3 hr. Recombinant interleukin 2 (rIL-2; Cetus) had little effect on c-myc expression but, in combination with PHA, it augmented levels of c-myc transcripts measured at 24 hr but not at 3 hr. Adding various inhibitors of lymphocyte proliferation to PHA-stimulated cultures revealed that cyclosporin A, dexamethasone, and OKT11A antibody (anti-sheep erythrocyte receptor) diminished levels of c-myc mRNA measured at 3 hr and 24 hr, whereas anti-Tac (anti-IL-2-receptor) inhibited at 24 hr but not at 3 hr. Thus, cyclosporin A, dexamethasone, and OKT11A interfere with early events of T-cell activation, whereas anti-Tac acts later. Hydroxyurea and 42/6 antibody (anti-transferrin receptor), which impair the G1----S transition in cycling cells, failed to inhibit c-myc expression and instead delayed the decrease in c-myc mRNA levels that normally occurs with the onset of DNA synthesis. These data indicate that c-myc is regulated (in normal lymphocytes) at several points in the cell cycle.
