ALTERED ENZYME EXPRESSION IN " DIFFERENTIATED " MURINE NEUROBLASTOMA CELLS

Summary.-Out of 17 enzymes studied, only 9 were detectable by starch gel electro-phoresis in mouse neuroblastoma cells in culture. Prostaglandin E1 (PGE1) and 4(-3-butoxy-4-methoxybenzyl)-2-imidazolidinone (R020-1724), a specific inhibitor of cAMP phosphodiesterase, were used to induce " differentiation ". Lactate and 6-phosphogluconate dehydrogenases and adenylate kinase were expressed as single bands in untreated neuroblastoma and induced " differentiated " cells, but the electrophoretic mobility of these enzymes in PGEl-treated cells was slower than that in malignant and R020-1724-treated cells. Three bands of glucose 6-phosphate dehydrogenase were detectable in PGEl-treated cells, whereas the R020-1724-treated cells had two bands and the untreated neuroblastoma cells had only one band. Aldolase was also expressed as a single band; however, the activity of this enzyme was much higher in PGEl-treated cells, whereas the activity was barely detectable for R020-1724-treated and untreated neuroblastoma cells. Some of the enzymes which are present in vivo are absent in vitro. Alkaline phosphatase is present in brain but is absent in neuroblastoma cells in vivo and in vitro. Two bands each of triose phosphate isomerase, fumarase and aldolase are present in brain, but only one band of these enzymes is present in neuroblastoma cells. Although PGE1 and R020-1724 induce many differentiated functions in neuroblastoma cells in a similar manner, PGE1 appears to change characteristically the expression of several enzymes. AN ELEVATION of the initracellular level of cAMP in neuroblastoma cells in culture induces many differentiated functions which are characteristic ofmature neurons. These include formation of long neurites, (Prasad and Hsie, 1971) increase in size of soma and nucleus associated with an increase in total RNA (Augusti-Tocco, et al., 1973; Prasad et al., 1973) blockade of cells in Gl-phase of cell cycle, (Prasad et al., 1973), increase in activities of tyrosine hydroxylase, (Richelson, 1973; Waymire, Weiner and Prasad, 1.972) choline acetyl