Interferon enhances 2-5A synthetase in embryonal carcinoma cells

Mouse teratocarcinomas provide a useful model of mammalian differentiation, because the malignant embryonal carcinoma (EC) stem cells of such tumours may produce various differential cell types in vivo or in vitro. Many EC cell lines have now been established and classified on the basis of their ability to differentiate in vivo into cell types characteristically derived from any of the three germ layers. There is convincing evidence that EC cells can neither produce interferon, nor respond to it by becoming resistant to virus, whereas differentiated cells derived from EC lines behave normally in both respects. We investigated the lack of responsiveness of EC cells towards interferon by measuring the levels of two double-stranded RNA-dependent enzyme activities recently shown to be enhanced by interferon. We report here that on treatment with interferon, EC cells show increased 2-5A synthetase levels comparable to those found in differentiated cells, while there is little or no effect on kinase activity in EC cells, in contrast to their differentiated counterparts.     

Sequential activation of HOX2 homeobox genes by retinoic acid in human embryonal carcinoma cells

RETINOIC acid had been implicated as a natural morphogen in chicken and frog embryogenesis, and is presumed to act through the gene regulatory activity of a family of nuclear receptors. Homeobox genes, which specify positional information in Drosophila and possibly in vertebrate embryogenesis, are among the candidate responsive genes. We previously reported that retinoic acid specifically induces human homeobox gene (HOX) expression in the embryonal carcinoma cell line NT2/D1. We now show that the nine genes of the HOX2 cluster are differentially activated in NT2/D1 cells exposed to retinoic acid concentrations ranging from 10(-8) to 10(-5) M. Genes located in the 3' half of the cluster are induced at peak levels by 10(-8) M retinoic acid, whereas a concentration of 10(-6) to 10(-5) M is required to fully activate 5' genes. At both high and low retinoic acid concentrations, HOX2 genes are sequentially activated in embryonal carcinoma cells in the 3' to 5' direction.