Adrenocortical cell proliferation in a cell transplantation model: The role of SV40 T antigen

Bovine adrenocortical cells immortalized by human telomerase reverse transcriptase (hTERT) are capable of forming functional vascularized tissue structures when transplanted in immunodeficient mice. These tissues maintain the life of adrenalectomized animals, show normal cell proliferation rates, and maintain a constant tissue size. These experiments were performed by co-transfection of an hTERT-encoding plasmid with an SV40 T antigen-encoding plasmid, but in tissues formed from clones derived in this way SV40 T Ag was not expressed. However, when tissues were formed from non- clonal heterogeneous populations of transfected cells, nodules of SV40 TAg-expressing cells arose that showed a high proliferation rate. These structures resembled nodules formed from transplanted bovine adrenocortical cells in which SV40 TAg was introduced by retroviral transduction rather than transfection. The reasons for these phenomena are discussed; in a nonclonal mixed population of cells, some may have much higher levels of SV40 TAg, which perturbs the normal histology and behavior of tissues formed from hTERT-immortalized adrenocortical cells.