Human Teratocarcinomas and Retinoic Acid-Mediated Tumor Differentiation

Biological differences exist between murine and human teratocarcinomas. A comparison of the regulated expression of retinoic nuclear receptor in RA-sensitive and retinoic acid (RA)-resistant teratocarcinomas may provide insight into the role these receptors play in human teratocarcinoma differentiation. Several laboratories have investigated changes in expression of important growth-regulated genes following RA treatment of cultured human teratocarcinomas. RA acts on the proliferative and tumorigenic potential of NT2/D1 cells. Using established germ cell tumor cell lines that are responsive to the effects of RA, genes are identified that might regulate important aspects of human teratocarcinoma growth or differentiation. The antitumor activity of trans-RA in chemotherapy refractory germ cell cancer is being studied in a clinical trial. The RA-mediated regulation of these transcription factors implicates these DNA-binding proteins as candidate signals that activate critical target genes controlling human teratocarcinoma differentiation.