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 (hc) and a 40-kDa light chain (lc), and is strongly expressed on the cell surface of various tumor cells, irrespective of their tissue of origin. We have recently demonstrated that overexpression of the CD98hc cDNA causes malignant transformation of NIH3T3 cells. To investigate the function of the extracellular domain of CD98hc in cell proliferation and malignant transformation, we established two NIH3T3-derived clones transfected with human truncated CD98hc cDNAs, and compared their characteristics with parental NIH3T3 and clones transfected with full-length CD98hc cDNA. Truncated as well as full-length CD98hc-transfected clones grew to a higher saturation density than control cells. Efficiency of colony formation in soft agar was augmented in all CD98hc-transfected clones, and the degrees of augmented 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 CD98hc 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-transfected clones was faster than that of full-length CD98hc-transfected clones.
Hara
K
K
Molecular Cell Biology Laboratory, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba Aramaki, Aoba-ku, Sendai, Miyagi 980-8578, Japan.
Kudoh
H
H
Enomoto
T
T
Hashimoto
Y
Y
Masuko
T
T
D016475:3T3 Cells; D000818:Animals; D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism; D000954:Antigens, Surface / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D018929:Cell Culture Techniques; D002455:Cell Division; D002461:Cell Line, Transformed; D027261:Fusion Regulatory Protein-1; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009374:Neoplasms, Experimental / Q000235:genetics* / Q000473:pathology; D010641:Phenotype; D017434:Protein Structure, Tertiary; D017384:Sequence Deletion; D014162:Transfection
D015703:Antigens, CD; D000954:Antigens, Surface; D002352:Carrier Proteins; D027261:Fusion Regulatory Protein-1; D009363:Neoplasm Proteins