Modulation of tumor immunogenicity of rat glioma cells by s-Myc expression: eradication of rat gliomas in vivo.
The Myc family proteins represented by c-Myc are thought to play a crucial role in cellular proliferation, differentiation, transformation, and apoptosis. In this study, we demonstrated the novel role for a Myc family protein in elicitation of immunogenic phenotypes in tumor cells. Injection of rat 9L or C6 glioma cells, together with the s-myc gene linked to the cytomegalovirus promoter, completely prevented formation of both brain tumors and s.c. tumors derived from the parental glioma cells. However, introduction of the s-myc gene had no inhibitory effect on development of B104-derived neuroblastoma. In addition, unlike the s-myc gene, injection of the c-myc or wild type p53 (wt-p53) gene together with glioma cells did not modulate the tumor immunogenicity and resulted in formation of gliomas in the animals. These findings suggest that s-Myc expression may stimulate the presentation of a tumor antigen common to 9L and C6 cells to T lymphocytes and augment the activity of the host immune system, resulting in prevention of glioma formation in vivo. This success in tumor eradication indicates the possibility of application of the s-myc gene for gene therapy of human brain tumors.
Asai
A
A
Biophysics Division, National Cancer Center Research Institute, Tokyo, Japan.
Miyagi
Y
Y
Hashimoto
H
H
Lee
S H
SH
Mishima
K
K
Sugiyama
A
A
Tanaka
H
H
Mochizuki
T
T
Yasuda
T
T
Kuchino
Y
Y
D000818:Animals; D001932:Brain Neoplasms / Q000276:immunology / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D016259:Genes, myc / Q000502:physiology; D016158:Genes, p53 / Q000502:physiology; D015316:Genetic Therapy; D005910:Glioma / Q000276:immunology / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D006614:Hindlimb; D008297:Male; D009368:Neoplasm Transplantation; D009447:Neuroblastoma / Q000276:immunology / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D010714:Phosphatidylethanolamines; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D051381:Rats; D011916:Rats, Inbred F344; D012878:Skin Neoplasms / Q000473:pathology; D014162:Transfection; D014407:Tumor Cells, Cultured
D010714:Phosphatidylethanolamines; D016271:Proto-Oncogene Proteins c-myc; C020888:1,2-dielaidoylphosphatidylethanolamine