Murine neurofibroma reversion by antisense RNA for HTLV-I tax

Neurofibroma cell lines derived from mice transgenic for HTLV-I LTR tax exp ress high levels of HTLVI tax mRNA and protein and exhibit a transformed ph enotype. A retrovirus vector carrying HTLV-I tax cDNA in reversed transcrip tional orientation was stably transfected into the neurofibroma cells. Anti sense RNA inhibited expression of the tax gene with a decrease of more than 40% in both tax mRNA and protein. Tax antisense RNA reversed the transform ed phenotype as exhibited by dramatic changes in cell morphology and growth characteristics. Expression of several cellular genes which are activated by Tax protein including GM-CSF, IL-6, LT/TNF, c-myc and LIF was down-regul ated, while M-CSF and c-src proto-oncogene expressions were up-regulated. A ccumulation of p-actin mRNA was not affected. The changes that occurred in the tax antisense expressing neurofibroma cells could be the consequence of the decreased concentration of Tax protein. These results also indicate th at HTLV-I Tax protein is crucial for maintaining the transformed cell morph ology, growth and proliferation of murine neurofibroma cells and suggest th at deregulation of endogenous cellular genes by Tax protein is the mechanis m through which neurofibromas occur in tax mice.