Expression of H–2, laminin and SV40T and TASA on differentiation of transformed murine teratocarcinoma cells

Abstract

Murine embryonal carcinoma cells (ECCs) do not express antigens of the major histocompatibility complex (H–2)^1,2, but do express cell-surface molecules shared with early embryos³. ECCs are also characterized by their insusceptibility to infection by various oncogenic viruses^4-7, and their ability to differentiate into a variety of adult cell types⁸. Differentiation of ECCs in vitro can occur spontaneously or can be induced^9–12. On exposure to retinoic acid the ECC line F9 (ref. 13) differentiates into cells which have the characteristics of parietal endoderm^10,14. When ECCs are exposed to simian virus 40 (SV40), the SV40 tumour (T) antigen is not expressed⁴, although the virus genome reaches the nucleus¹⁵, and a primary transcript of the SV40 A gene is made¹⁶. However, following exposure to retinoic acid, the differentiated cells, like most mouse somatic cells, are susceptible to SV40 abortive infection and synthesize large T and small t antigens¹⁷. To monitor the molecular events associated with the expression of the SV40 A gene on differentiation, we have constructed an ECC line (F9 12–1) containing a single integrated copy of the SV40 genome¹⁸. This was accomplished by introducing a recombinant plasmid consisting of pBR322 linked to the herpes simplex type 1 thymidine kinase gene and SV40 genome¹⁸ into a thymidine kinase-deficient F9 cell line¹⁹. We report here that in F9 12–1 cells exposed to retinoic acid, synthesis of the SV40 A gene product(s), T and tumour-associated specific antigens (TASA), parallels the appearance of the normal hallmarks of differentiation in this cell line, H–2 antigens and the basement membrane protein laminin²⁰.