Restoration of a tumorigenic phenotype by beta 2-microglobulin transfection to EL-4 mutant cells.
It has frequently been suggested that loss of beta 2-microglobulin (beta 2m) in tumor cells may lead to malignant progression due to escape from immunological recognition. Here, we directly tested the role of beta 2m expression in tumorigenicity. A beta 2 m loss mutant (C4.4-25-), selected from the murine lymphoma EL-4, showed a marked reduction in tumorigenicity as compared with EL-4 in normal C57B1/6 (B6) mice. The reduced tumorigenicity was directly related to beta 2 m expression. Transfection of an intact murine beta 2m gene markedly increased the tumorigenic potential. The reduced tumorigenicity of C4.4-25- compared with beta 2m transfected cells was observed also in athymic B6 nu/nu mice, but was abolished in B6 mice depleted of natural killer (NK) 1.1-positive cells. These results show that restoration of beta 2m expression can promote tumorigenicity and demonstrate for the first time that induction of major histocompatibility complex class I expression by transfection can lead to escape from NK cells in vivo.
Glas
R
R
Department of Tumor Biology, Karolinska Institutet, Stockholm, Sweden.
Sturmhöfel
K
K
Hämmerling
G J
GJ
Kärre
K
K
Ljunggren
H G
HG
D000818:Animals; D002469:Cell Separation; D005434:Flow Cytometry; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009154:Mutation; D010641:Phenotype; D014162:Transfection; D014407:Tumor Cells, Cultured; D001613:beta 2-Microglobulin / Q000235:genetics*
D001613:beta 2-Microglobulin