Isolation of the genes involved in the process of differentiation inhibition and apoptosis induced by PU.1 in murine erythroleukemia cells

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PU.1 is a transcription factor essential for development of myelomonocytes and B cells. In murine erythroleukemia (MEL) cells, PU.1 is expressed as the result of degenerated activation of the PU.1 gene. We previously showed that overexpression of PU.1 in MEL cells in the presence of differentiation-inducing reagent, DMSO, results in apoptosis but not differentiation of the cells. In the present study, by using the differential display strategy, we isolated 100 of known and 151 of unknown genes whose expression is changed in the process of PU.1-mediated differentiation inhibition and apoptosis in MEL cells.The category of genes whose expression is up-regulated included some genes known to be implicated in regulation of cell cycle and/or cell proliferation and to be expressed normally in myelomonocyte- and B cell-lineage. The category of genes whose expression is down-regulated included some genes known to be important for function of mitochondria and ribosome and to be implicated in differentiation and survival of neural cells. It was also found that expression of a wide variety of myelomonocyte- and B cell-specific genes other than identified by differential display was up-regulated. Moreover, the cells became adherent and phagocytic after overexpression of PU.1, and the apoptosis was avoided, if not completely, by addition of myeloid growth factors such as GM-CSC and M-CSF to the culture. In addition, we are now trying to isolate the full length cDNA of the unknown genes identified.Taken together, in this study, we identified some genes involved in differentiation inhibition and apoptosis in MEL cells and provided an evidence of lineage switching of MEL cells by PU.1 which might be one of the reasons for differentiation inhibition of the cells.