Iron specific growth inhibition of Burkitt's lymphoma cells in vitro, associated with a decrease in translocated c-myc expression.
The cellular proto-oncogene c-myc is an important transcription factor that plays a role in several cellular activities such as proliferation, differentiation, and apoptosis. It follows that regulation of c-myc expression is crucial for maintaining cell integrity. Amplification or translocation can convert this proto-oncogene into an activated oncogene, thereby deregulating c-myc expression. Changes in the expression of c-myc leading to malignant cell growth and tumor progression can also be triggered by extrinsic factors. It has been reported that iron can increase cell proliferation, mainly by stimulating DNA synthesis as well as by enhancing c-myc expression. Here, we studied the effect of iron on cells in which c-myc expression is deregulated by either chromosomal translocation or gene amplification. When added to Burkitt's lymphoma cell lines, iron markedly inhibits cell proliferation. This effect is mediated by a cell cycle arrest in G2/M, followed by an important decrease in c-myc expression, whereas no effect could be observed in a cell line harboring amplified c-myc. Moreover, the down-regulation of c-myc expression, which is independent from cell cycle blockade, leads to cell death by apoptosis. Collectively, our results suggest the existence of a novel iron-dependent cell cycle regulatory mechanism involving modulation of translocated c-myc gene expression.
Héma-Québec, Recherche et Développement, route du Vallon, Sainte-Foy, Québec, Canada.
Marie-Eve
ME
Habel
Réal
R
Lemieux
Daniel
D
Jung
D017209:Apoptosis / Q000187:drug effects; D002051:Burkitt Lymphoma / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007501:Iron / Q000633:toxicity*; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics* / Q000378:metabolism; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D014178:Translocation, Genetic
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D007501:Iron