AUGMENTATION OF C-FOS AND C-JUN EXPRESSION IN TRANSGENIC MICE CARRYING THE HUMAN T-CELL LEUKEMIA-VIRUS TYPE-I TAX GENE

To analyze the effect of human T-cell leukemia virus type I (HTLV-I) o n cellular gene expression and its relation to tumorigenesis, two line s of transgenic mice carrying the long terminal repeat (LTR)-env-pX-LT R regions of the HTLV-I genome were produced. The transgene was expres sed in many organs, including the brain, salivary gland, spleen, thymu s, skin, muscle, and mammary gland. We found that the expression of th e c-fos and c-jun genes, but not of the lyn and c-myc genes, was augme nted 2- to 20-fold in histologically normal skin and muscle of these m ice. The augmentation was tissue specific, suggesting the involvement of a cellular factor in the transgene action. In these mice, a three t o seven times higher incidence of tumors was seen as compared with the control mice. These tumors included mesenchymal tumors, such as fibro sarcoma, neurofibroma, and lipoma, and adenocarcinomas of the mammary gland, salivary gland, and lung. The c-fos and c-jun genes were also a ctivated in these tumors. The possible roles of elevated c-fos and c-j un gene expression in tumorigensis are discussed.