c-Myc over-expression in Ramos Burkitt's lymphoma cell line predisposes to iron homeostasis disruption in vitro.
Burkitt's lymphoma is an aggressive B-cell neoplasm resulting from deregulated c-myc expression. We have previously shown that proliferation of Burkitt's lymphoma cell lines such as Ramos is markedly reduced by iron treatment. It has been shown that iron induces expression of c-myc which, owing to its transcriptional regulatory functions, regulates genes involved in iron metabolism. Transient enhancement of c-myc expression by iron could increase the expression of genes involved in iron incorporation, which could lead to an accumulation of intracellular free iron. Here, we have investigated whether cells with a high basal level of c-Myc were more likely to accumulate free iron. Our results suggest that the basal level of c-Myc in Ramos cells is twofold higher than what is seen in HL-60 cells. Moreover, in Ramos cells, where c-Myc is expressed at a high level, H-ferritin expression is down-regulated, transferrin receptor (CD71) expression is increased, and ferritin translation is inhibited. These modifications in iron metabolism, resulting from the strong basal expression of c-Myc, and amplified by iron addition, could lead to a disruption in homeostasis and consequently to growth arrest.
Habel
Marie-Eve
ME
Héma-Québec, Recherche et Développement, 1009 route du Vallon, Sainte-Foy, Quebec, Canada G1V 5C3.
Jung
Daniel
D
D015703:Antigens, CD / Q000235:genetics; D002051:Burkitt Lymphoma / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation; D005293:Ferritins / Q000096:biosynthesis; D015972:Gene Expression Regulation, Neoplastic; D018922:HL-60 Cells; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D007501:Iron / Q000378:metabolism* / Q000494:pharmacology; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis* / Q000502:physiology; D011990:Receptors, Transferrin / Q000235:genetics
D015703:Antigens, CD; C068126:CD71 antigen; D016271:Proto-Oncogene Proteins c-myc; D011990:Receptors, Transferrin; D005293:Ferritins; D007501:Iron