Conditional immortalization and/or transformation of rat cells carrying v-abl or EJras oncogene in the presence or absence of glucocorticoid hormone

Abstract

Early‐passaged rat chondroblasts (RX cells) and embryonal fibroblasts (RE cells) are hardly transformed by transfection of activated human H‐ras (EJras) or by Abelson murine leukemia virus v‐abl oncogene. However, these cells were transformed by v‐abl or EJras gene when dexamethasone (DX) was added in the culture medium as well as when co‐transfected with retrovirus LTR‐linked mouse c‐myc gene. RX cell lines carrying v‐abl (RXabl), RE cell lines carrying v‐abl (REabl) and RX cell lines carrying EJras (RXEJ) were established from transformed colonies in the DX‐added soft agar. In the absence and in the presence of DX, RXabl cells showed mortal and immortalized, REabl cells showed mortal and transformed, and RXEJ cells showed immortalized and transformed phenotypes, respectively. Especially, immortalization and transformation of REab11 and REab13 lines were switched on and off by addition and depletion of DX. v‐abl or EJras mRNA levels in tested REabl, RXabl and RXEJ lines cultured without DX was not decreased compared to those cultured with the hormone. The above suggests that, like myc gene, glucocorticoid collaborates with v‐abl or activated ras oncogene to transform unestablished rat cells and that the transformation phenotypes were determined not only by the introduced oncogene but by the cellular condition including their tissue origin. Transformation of senescent REabl cells in the absence of DX was tested by transfecting different oncogenes. Among nuclear oncogenes tested, only adenovirus 12 E1A gene could induce transformation of G₀‐arrested REabl cells in a cooperative fashion with the integrated v‐abl gene.