Modulation of prion protein gene expression by growth factors in cultured mouse astrocytes and PC-12 cells.
The present study was performed on primary cultures of mouse astrocytes and cultures of rat pheochromocytoma PC-12 in order to investigate the regulation of the prion protein (PrP) gene expression in relation to proliferation and differentiation. Treatment of PC-12 cells with interleukin-6 (IL-6) and beta-nerve growth factor (NGF) resulted in induction of neuronal differentiation. Northern blot analysis demonstrated a 4-fold increase of PrP mRNA in relation to cellular differentiation, after 7 days of treatment with either of the two factors. In astrocytes, PrP and glial fibrillary acidic protein (GFAP) mRNA levels were found to be regulated in a similar manner during development in vitro. A 3-fold increase of their mRNAs was observed from 5 to 14 days of culture (proliferation period). Then, their gene expressions showed a slight decrease from 14 to 28 days (maturation period). Treatment of astrocytes with IL-6, basic fibroblast growth factor (bFGF), and epidermal growth factor (EGF) appeared to markedly down-regulate the expression of GFAP mRNAs, which might reflect cell maturation. In contrast, they had no significant effect on the expression of PrP gene. These results suggest that the PrP gene expression is differently regulated in neural cells. In neuronal cells, it is mainly associated with differentiation. On the other hand, in astrocytes, the PrP mRNA level seems to be not only related to the proliferation and differentiation stages.