T-antigen regulated expression reduces apoptosis of Tag-transformed human myoblasts

The generation of human myogenic cell lines could potentially provide a val uable source for cell transplantation in myopathies. The dysregulation of p roliferative-differentiative signals by viral oncogenes can result in the i nduction of apoptosis. Whether apoptosis occurred in myogenic cells express ing large T antigen (Tag) from SV40 upon differentiation was unknown. Human muscle satellite cells were transfected with two different constructs, con taining either an origin-defective SV40 genome or Tag under vimentin promot er control. When differentiation was triggered, Tag expression reduced the formation was of myotubes and dead cells showing apoptotic features were pr esent. However, the cells expressing SV40 Tag under vimentin promoter contr ol retained their capacity to form myotubes and expressed the myofibrillar proteins as myosin heavy chain and dystrophin when Tag expression was silen t. Their apoptotic rate was similar to that of untransfected cells. The obs ervation that apoptosis can be prevented by the down-regulation of Tag sugg ests that the programmed cell death induced in transformed cells can be rev ersed, and confirms the regulatory efficiency of the human vimentin promote r.