Tax protein of human T-cell leukemia virus type I is required for maintenance of the transformed phenotype.

We have isolated and characterized revertants of a clonal cell line (40MRatcl-1) of human T-cell leukemia virus type I Tax-transformed Rat1 cells. The 40MRatcl-1 cells contain a single copy of tax gene, form large colonies in soft agar, elicit tumors rapidly in nude mice and revert to the normal phenotype at low frequency. From one of its subclones (B7) bearing pSV2gpt DNA as a marker gene, four morphologically reverse-transformed cell lines were isolated. They display contact inhibition at confluency, lose the ability to form colonies in soft agar, fail to form tumors in nude mice and restore the transformed phenotype similar to that of 40MRatcl-1 cells by transfection with the tax-expression plasmid. Southern blot analysis revealed that they have lost the tax gene. Our results indicate that transformation of Rat1 cells by Tax is not the consequence of secondary mutations of cellular genes and that tax functions are directly required for establishment and maintenance of the transformed phenotype.