Bone morphogenetic proteins and retinoic acid induce human endogenous retrovirus HERV-K expression in NT2D1 human embryonal carcinoma cells.

Expression of the HERV-K human endogenous retrovirus is very low in normal and tumor tissue, but is readily detected in testicular germ cell tumors (TGCT). NT2D1 human embryonal carcinoma cells represent in vitro models for the stem cells of TGCT, and can be differentiated by treatment with bone morphogenetic proteins (BMP) or retinoic acid (RA). In a search for BMP target genes in NT2D1 cells, HERV-K was identified as an early BMP and RA target. It was shown that HERV-K expression was induced upon treatment of NT2D1 cells with BMP or with RA, but not with activin or transforming growth factor (TGF)-beta. Induction of HERV-K expression was rapid but transient, with transcripts becoming undetectable in differentiated NT2D1 cultures. Thus NT2D1 cells provide a suitable in vitro system for the study of the factors controlling HERV-K expression during cellular differentiation, which may play a role in HERV-K expression in TGCT.