Abstract
The c-myc proto-oncogene is involved in the control of cellular proliferation and differentiation (for review see Cole 1986). Its deregulated expression, caused by chromosomal translocation (Dalla-Favera 1982, 1983; Taub 1982), amplification (Collins and Groudine 1982; Dalla-Favera 1982) or retroviral insertion (Hayward 1981), is associated with lymphoid and non-lymphoid malignancies in different species. The mechanism regulating normal c-myc gene expression and the cause of its deregulation in tumor cells remains largely unknown. Since normal c-myc alleles are down-regulated in the presence of constitutively expressed c-myc oncogenes in naturally occurring tumors (Leder 1983) as well as in in vitro transformed cells (Rapp 1985; Lombardi 1987) and transgenic mice (Adams 1985), it has been frequently suggested that c-myc expression may be under the control of negative feed-back regulation. However, the actual existence of such a regulatory function remains controversial and its mechanism of action unknown. In an attempt to clarify these issues we have characterized a negative feed-back loop regulating c-myc expression in human EBV-immortalized lymphoblastoid cells and then comprehensively investigated the activity of this mechanism in a number of cell types. Our results provide direct evidence for the existence of a dose-dependent negative feed-back loop and preliminarily define its mechanism. However, we find that this mechanism is inactive in all tumor cell lines tested derived from a variety tissues, suggesting that its inactivation may represent a general regulatory disturbance of transformed cells.
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© 1990 Springer-Verlag Berlin Heidelberg
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Lombardi, L., Grignani, F., Sternas, L., Cechova, K., Inghirami, G., Dalla-Favera, R. (1990). Mechanism of Negative Feed-back Regulation of c-myc Gene Expression in B-Cells and its Inactivation in Tumor Cells. In: Potter, M., Melchers, F. (eds) Mechanisms in B-Cell Neoplasia 1990. Current Topics in Microbiology and Immunology, vol 166. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-75889-8_36
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DOI: https://doi.org/10.1007/978-3-642-75889-8_36
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