Malignant transformation of NIH3T3 cells by overexpression of early lymphocyte activation antigen CD98

CD98, which forms a heterodimer of relative molecular mass (M-r) 125, 000, was originally identified as an early T cell activation antigen. It consists of a heavy chain of M-r 85,000 that bears the CD98 epitope and a light chain of M-r 40, 000. CD98 is strongly expressed on the surface of activated lymphocytes and various tumor cells irrespective of tissue origins. To investigate the participation of CD98 in cellular proliferation and malignant transformation, we established and characterized human CD98-transfected NIH3T3 clones. Although the doubling times of the control cells and CD98-transfected clones were almost the same, CD98-transfected clones grew to a higher saturation density than control cells. Efficiency of colony formation in soft agar was augmented in CD98-transfected clones, and this augmentation was significantly reduced by antihuman CD98 mAb. Furthermore, CD98-transfected clones developed tumors in athymic mice. These results indicated that overexpression of CD98 participates in the process of malignant transformation, suggesting that CD98 has oncogenic potential. (C) 1999 Academic Press.