Dominant-negative p53 can restore tumorigenicity of L-929 cells in immunocompetent mice.
To study the effect of a transforming allele of the tumor suppressor p53 upon the anti-tumor immune response, antigenic L-929 cells were transfected with the dominant-negative valine135 mutant of murine p53. Several p53val135-expressing transfectants formed non-regressing tumors in immunocompetent hosts. The growth rates of tumorigenic and non-tumorigenic clones were equivalent in vitro in sublethally irradiated C3H/HeN mice and in nude mice. Tumorigenic and non-tumorigenic p53val135-expressing L-929 clones expressed equivalent levels of cell surface class I major histocompatibility complex (MHC) glycoproteins. Immunization with a tumorigenic Lp53val135 clone protected mice from subsequent challenge and primed MHC class I-restricted cytotoxic T-lymphocytic precursors. Secretion of an immunosuppressive cytokine, transforming growth factor beta-1 and sensitivity to tumor necrosis factor-alpha were equivalent from tumorigenic and non-tumorigenic cell lines. These data suggest that expression of a transforming allele of p53 can allow L-929 cells to escape the host immune system.
Appleman
L J
LJ
Department of Cell Biology, New York University School of Medicine, New York, USA.
Frey
A B
AB
D000483:Alleles; D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000276:immunology*; D005799:Genes, Dominant; D016158:Genes, p53; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis; D007121:Immunocompetence; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008819:Mice, Nude; D012878:Skin Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry* / Q000235:genetics* / Q000276:immunology
D015395:Histocompatibility Antigens Class I; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016159:Tumor Suppressor Protein p53