Enhanced tumorigenicity caused by truncation of the extracellular domain of GP125/CD98 heavy chain

GP125/CD98 is a heterodimeric 125-kDa glycoprotein, which consists of an 85 -kDa heavy chain the) and a 40-kDa light chain (Ic), and is strongly expres sed on the cell surface of various tumor cells, irrespective of their tissu e of origin. We have recently demonstrated that over-expression of the CD98 hc cDNA causes malignant transformation of NIH3T3 cells. To investigate the function of the extracellular domain of CD98hc in cell proliferation and m alignant transformation, we established two NIH3T3-derived clones transfect ed with human truncated CD98hc cDNAs, and compared their characteristics wi th parental NIH3T3 and clones transfected with full-length CD98hc cDNA, Tru ncated as well as full-length CD98hc-transfected clones grew to a higher sa turation density than control cells. Efficiency of colony formation in soft agar was augmented in all CD98hc-transfected clones, and the degrees of au gmented colony formation of the transfectants expressing full-length CD98hc of 529 a.a. or truncated CD98hc of 418 a,a, were reduced by anti-human CD9 8hc antibodies, while that of the transfectant expressing truncated CD98hc of 237 a,a, lacking the epitopes recognized by anti-human CD98hc antibodies was not affected by the addition of antibodies. CD98hc-transfected clones developed tumors in athymic mice, and tumor growth of truncated CD98hc-tran sfected clones was faster than that of full-length CD98hc-transfected clone s.