A nonkaryophilic T antigen of SV40 can either immortalize or transform rodent cells, and cooperates better with cytoplasmic than with nuclear oncoproteins

Abstract

We investigated the cell growth alterations brought about by a mutant nonkaryophilic large T antigen (NKLT) of SV40, alone and in combination with other oncogenes. NKLT by itself exhibited bivalent functional competence: it induced immortalization in early-passage rat embryo fibroblasts (REFs) and transformation in established NIH3T3 cells, although it was totally unable to transform nonestablished REFs. The absence of a normal small T reduced but did not suppress such effects. Coexpression of NKLT with the nuclear oncoprotein Polyoma large T significantly increased the efficiency of the same activities sustained by NKLT alone, but did not confer the ability to transform nonestablished REFs. Similar results were also observed in cells cotransfected with NKLT and another nuclear oncoprotein, E1A of adenovirus. In contrast, NKLT coexpression with either of the cytoplasmic oncoproteins, Polyoma middle T or activated Ha-ras, produced full transformation of early passage REFs. Thus the NKLT stimulus has the following properties: (i) it straddles the immortalizing/transforming distinction of oncogenic competence, (ii) it potentiates the effects of some nuclear oncoproteins, and (iii) it complements certain cytoplasmic oncoproteins to promote transformation of nonestablished cells.