Effect of Human Interferons on Morphological Differentiation and Suppression of N-mycGene Expression in Human Neuroblastoma Cells

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Abstract
The activity of human interferons (HuIFNs) to induce morphological changes and the suppression of N-myc gene expression on human neuroblastoma cells (GOTO and KP-N-RT) was evaluated. Morphological differentiation, characterized as the extension and bifurcation of neurites, the formation of multinucleated giant cells and the formation of neurite networks, was induced by treatment with recombinant HuIFN-.gamma. (rHuIFN-.gamma.) and also with natural HuIFN-.gamma. on human neuroblastoma cells (GOTO and KP-N-RT). But recombinant HuIFN-.alpha.A and recombinant HuIFN-.beta. did not induce any changes. The rHuIFN-.beta. and rHuIFN-.gamma. inhibited the growth of GOTO and KP-N-RT cells more strongly than the rHuIFN-.alpha.A did. The expression of N-myc gene was suppressed in GOTO cells treated with rHuIFN-.gamma.. The suppressive effect of rHuIFN-.gamma. was dependent on the duration of the treatment. However, rHuIFN-.alpha.A and rHuIFN-.beta. did not suppress N-myc gene expression. Moreover, both morphological differentiation and the suppressive effect on N-myc gene expression by rHuIFN-.gamma. were inhibited in the presence of cycloheximide. These results suggest that the morphological changes and N-myc gene expression in neuroblastoma cells are closely related. Furthermore, this decreased N-myc gene expression during the morphological differentiation may be related to the proteins induced by HuIFN-.gamma.

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