Expression patterns of the JEM-1 gene in normal and tumor cells: ubiquity contrasting with a faint, but retinoid-induced, mRNA expression in promyelocytic NB4 cells

Abstract

The JEM-1 gene, recently identified in acute promyelocytic leukemia (APL) cells, codes for a novel nuclear factor (Duprez et al Oncogene 1997; 14: 1563–1570). JEM-1 is kept silent in the APL cell line NB4, but up-regulated (3 kb transcript) during cell maturation. Here, we show that retinoic acid (RA)-induced JEM-1 expression is biphasic (peaks at 6 h and 48 h) and associated with the later stages of maturation. Retinoids, which cooperates with cAMP to induce maturation, also cooperates with cAMP to up-regulate JEM-1, either in maturation-responsive NB4 cells or in NB4-R1 resistant subclones. APL patients showed a low, yet variable, level of JEM-1 mRNA in bone marrow. RA treatment induced an increase in the level of JEM-1 mRNA, as detected by a semi-quantitative PCR. This increase can result from both gene up-regulation or replacement of leukemia cells by differentiated ones. Analysis of JEM-1 expression patterns in normal and tumor cells revealed that JEM-1 expression was ubiquitous. Cell lines derived from monocytic and erythroid leukemias, expressed low and high amounts of JEM-1 mRNA, respectively. Using a JEM cDNA probe, distinct profiles of expression and different transcript sizes (4 kb, 3 kb and 2 kb) were also identified in tumour and normal non-hematopoietic tissues, while interestingly only the 3 kb transcript was up-regulated in NB4 cells. This work identifies JEM-1 as a novel ubiquitous gene whose expression is low in APL cells, but can be restored by RA treatment, concomitant with cell maturation.