DOMINANT-NEGATIVE P53 CAN RESTORE TUMORIGENICITY OF L-929 CELLS IN IMMUNOCOMPETENT MICE

被引:8
作者
APPLEMAN, LJ
FREY, AB
机构
[1] NYU,MED CTR,SCH MED,DEPT CELL BIOL,NEW YORK,NY 10016
[2] NYU,KAPLAN CANC CTR,SCH MED,NEW YORK,NY 10016
关键词
D O I
10.1002/ijc.2910630419
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 valine(135) mutant of murine p53. Several p53(val135)-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 nontumorigenic p53(val135)-expressing L-929 clones expressed equivalent levels of cell surface class I major histocompatibility complex (MHC) glycoproteins. Immunization with a tumorigenic Lp53(val135) 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-ru 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. (C) 1995 Wiley-Liss, Inc.
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收藏
页码:576 / 583
页数:8
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