Strong immunogenicity is induced by antitumor triazene compounds in tumor cells through a mutagenic mechanism. A highly immunogenic 'D' clone, isolated from a dacarbazine-treated L5178Y leukemia of DBA/2 mice, was transfected with K-ras mutated at codon 12 (i.e. rasm12). This transfected clone presents at least 2 mutations, one concerning K-ras gene, and the other affecting an unrelated gene, responsible for the generation of a highly immunogenic, MHC class I restricted non-self peptide. The results indicate that cells of 'D' clone transfected with rasm12 were less immunogenic than cells of the same origin transfected with the vector alone. Moreover, rasm12)-transfected cells showed lower levels of H-2K(d) gene expression with respect to those detectable in control cells. In addition, in vivo and in vitro sensitization against 'D' clone carrying mutated ras did not result in a strong cytotoxic T lymphocyte response against rasm12-transfected non immunogenic L5178Y target cells. These preliminary results suggest that K-ras mutation could down-regulate the level of tumor immunogenicity, possibly acquired through a mutagenic process affecting other unrelated genes.

Testorelli, C., Bussini, S., De Filippi, R., Marelli, O., Orlando, L., Greiner, J.w., et al. (1997). Dacarbazine-induced immunogenicity of a murine leukemia is attenuated in cells transfected with mutated K-ras gene. JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH, 16(1), 15-22.

Dacarbazine-induced immunogenicity of a murine leukemia is attenuated in cells transfected with mutated K-ras gene

TENTORI, LUCIO;BONMASSAR, ENZO;GRAZIANI, GRAZIA
1997-01-01

Abstract

Strong immunogenicity is induced by antitumor triazene compounds in tumor cells through a mutagenic mechanism. A highly immunogenic 'D' clone, isolated from a dacarbazine-treated L5178Y leukemia of DBA/2 mice, was transfected with K-ras mutated at codon 12 (i.e. rasm12). This transfected clone presents at least 2 mutations, one concerning K-ras gene, and the other affecting an unrelated gene, responsible for the generation of a highly immunogenic, MHC class I restricted non-self peptide. The results indicate that cells of 'D' clone transfected with rasm12 were less immunogenic than cells of the same origin transfected with the vector alone. Moreover, rasm12)-transfected cells showed lower levels of H-2K(d) gene expression with respect to those detectable in control cells. In addition, in vivo and in vitro sensitization against 'D' clone carrying mutated ras did not result in a strong cytotoxic T lymphocyte response against rasm12-transfected non immunogenic L5178Y target cells. These preliminary results suggest that K-ras mutation could down-regulate the level of tumor immunogenicity, possibly acquired through a mutagenic process affecting other unrelated genes.
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore BIO/14
English
Con Impact Factor ISI
immunogenicity; K-ras; leukemia; mutated oncogene; triazenes; xenogenization
Testorelli, C., Bussini, S., De Filippi, R., Marelli, O., Orlando, L., Greiner, J.w., et al. (1997). Dacarbazine-induced immunogenicity of a murine leukemia is attenuated in cells transfected with mutated K-ras gene. JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH, 16(1), 15-22.
Testorelli, C; Bussini, S; De Filippi, R; Marelli, O; Orlando, L; Greiner, Jw; Grohmann, U; Tentori, L; Giuliani, A; Bonmassar, E; Graziani, G
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/52878
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