K. Hara et al., Enhanced tumorigenicity caused by truncation of the extracellular domain of GP125/CD98 heavy chain, ONCOGENE, 19(54), 2000, pp. 6209-6215
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.