Monocytic differentiation of cultured leukemic cells HL60 can be induced by a variety of compounds including analogs of vitamin D3. We studied the expression of oncogenes c-fos, c-fms, c-fes, c-myb, c-myc, and c-Ha-ras during this process, and attempted to relate these and a conventional marker of monocytic differentiation, the nonspecific esterase activity to changes in cytosol levels of the Ca2+-binding proteins. The analogs of vitamin D3, 1α,25-dihydroxycholecalciferol, 1α,25-dihydroxy-26,27-hexafluorocholecalciferol, and 1α,25-dihydroxy-24R-fluorocholecalciferol, reduced the total calcium binding activity and the cellular levels of calmodulin, but calbindin(28k) could not be detected in HL 60 cells. A correlation was evident between the potency of these compounds as inducers of differentiation demonstrated by nonspecific esterase activity, the degree of reduction in calmodulin concentration, the rate of the inhibition of DNA synthesis and of expression of c-myc and c-myb genes, and the induction of the expression of oncogenes c-fos and c-fms. These experiments indicate that the events which underlie monocytic differentiation of HL 60 cells can be observed to occur in discrete steps which include an inhibition of DNA synthesis, a reduction of cellular levels of calmodulin, and altered expression of several oncogenes.
|Original language||English (US)|
|Number of pages||7|
|State||Published - Jan 1 1986|
All Science Journal Classification (ASJC) codes
- Pathology and Forensic Medicine
- Molecular Biology
- Cell Biology