Disruption of the putative c-myc auto-regulation mechanism in a human B cell line.

Abstract

It has been proposed that excessive or temporally inappropriate expression of the c-myc proto-oncogene determines a genetic program for cells that directs them toward proliferation, and away from differentiation. In support of this proposal, constitutive expression of c-myc in either murine erythroleukaemia cells, or 3T3-L1 cells largely prevents the progression of their respective differentiation schedules(1,2). Additionally, when resting cells of numerous types are treated with various mitogens, proliferation is preceded by rapid induction of c-myc expression (3,4). The inductive role that the mitogens play in proliferation can be in part substituted for by c-myc (5). An issue that remains outstanding is how the induction of c-myc is controlled. It has been theorised that c-myc auto-regulates its own transcription (6). This was provoked by the observation that in Burkitts lymphoma (BL), there is de-regulated expression of c-myc derived from the translocated allele, whilst the unrearranged allele is generally silent (6). This situation was to some extent re-capitulated by Lombardi et al (7) who witnessed the down-regulation of c-myc genes in human B cell lines into which they had stably introduced de-regulated c-myc. Because the products of the c-myc gene are two nuclear phosphoproteins with DNA-binding capacity, it has been considered that the auto-regulation is direct, requiring only the c-myc product and the c-myc template. Alternatively, the effect may be indirect, operating via pathways that may be disrupted and hence rendered inoperative in certain cell types. In order to examine this, we have investigated the generality of auto-regulation. Here we report an established human B cell line that is not susceptible to auto-regulation.KeywordsBurkitts LymphomaBurkitts LymphomaNuclear PhosphoproteinCell BioIMetallothionein PromoterThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.