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.
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 3kb 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.
Tong
J H
JH
Institut National de la Santé et de la Recherche Médicale, INSERM-U496, Institut Universitaire d'Hématologie, Hôpital Saint-Louis, Paris, France.
Fant
X
X
Duprez
E
E
Benoit
G
G
Uphoff
C C
CC
Drexler
H G
HG
Pla
J C
JC
Lofvenberg
E
E
Lanotte
M
M
D000328:Adult; D001483:Base Sequence; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D002478:Cells, Cultured; D002878:Chromosomes, Human, Pair 1; D017931:DNA Primers; D005333:Fetus; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics* / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D012176:Retinoids / Q000494:pharmacology*; D014157:Transcription Factors / Q000235:genetics*; D014407:Tumor Cells, Cultured
C105528:BLZF1 protein, human; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D017931:DNA Primers; D009687:Nuclear Proteins; D012333:RNA, Messenger; D012176:Retinoids; D014157:Transcription Factors