Deregulated c-myc expression overrides IFN gamma-induced macrophage growth arrest.

Autor: Vairo G; University of Melbourne, Department of Medicine, Royal Melbourne Hospital, Parkville, Australia., Vadiveloo PK, Royston AK, Rockman SP, Rock CO, Jackowski S, Hamilton JA
Jazyk: angličtina
Zdroj: Oncogene [Oncogene] 1995 May 18; Vol. 10 (10), pp. 1969-76.
Abstrakt: Induction of c-myc gene expression is an essential response to growth promoting agents, including colony-stimulating factor 1 (CSF-1). Down regulation of c-myc expression occurs in response to a variety of negative growth regulators in many cell types. However, for many of these systems the causal link between c-myc down regulation and growth arrest remains to be established. Here we show for CSF-1-dependent BAC1.2F5 mouse macrophages that interferon-gamma (IFN gamma) results in a midlate G1 phase decrease of CSF-1-dependent c-myc mRNA and subsequent cell cycle arrest. Introduction of a deregulated c-myc gene into these cells, which prevents the IFN gamma-mediated decrease in c-myc expression, overrides the cell cycle arrest and restores CSF-1-dependent growth in the presence of the cytokine. This result contrasts with the macrophage growth arrest induced by cAMP elevation, which also suppresses c-myc expression, but is not overcome by a deregulated c-myc gene. These results show that inhibition of c-myc expression is an essential component in IFN gamma-mediated cell cycle arrest and demonstrates that distinct mechanisms contribute to IFN gamma- and cAMP-mediated growth arrest in macrophages.
Databáze: MEDLINE