MODULATION OF C-MYC, C-MYB, C-FOS, C-SIS AND C-FMS PROTOONCOGENE EXPRESSION AND OF CSF-1 TRANSCRIPTS AND PROTEIN BY PHORBOL DIESTER IN HUMAN-MALIGNANT HISTIOCYTOSIS DEL CELL-LINE WITH 5Q-35 BREAK POINT

Following exposure to phorbol ester (TPA), DEL cell line, a human mali gnant histiocytosis (MH) cell line, is able to differentiate along a m acrophage phenotype and thus it provides a suitable model for analyzin g the sequential and differential gene expression associated with mono cyte/macrophage differentiation. C-myc, c-myb, c-fos, c-sis and c-fms expression were determined by Northern analysis at various times follo wing TPA treatment. The results showed that TPA down-modulated the con stitutive expression of c-myc, c-myb, and c-fins, mRNA to low but stil l detectable levels. Conversely, TPA-induced differentiation resulted in transient appearance of c-fos, whereas no change in the level of c- sis and actin transcripts were observed. Thus, the c-fms and c-sis gen es appear to be regulated in a specific manner in this malignant histi ocytosis derived cell line. Furthermore, these investigations demonstr ated a constitutive CSF-1 gene expression which transiently increased at mRNA and also at protein level as evaluated by a murine bone marrow CFU bioassay. Through this drug-induced modulation, the DEL cell line offers an additional model for studying some of the subtle interrelat ions existing between a growth factor (CSF-1) and its receptor (c-fms) in the monocyte/macrophage system.