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Activation of ras oncogenes and expression of tumor‐specific transplantation antigens in methylcholanthrene‐induced murine fibrosarcomas
Author(s) -
Carbone Giusi,
Borrello Maria Grazia,
Molla Alessandra,
Rizzetti Maria Grazia,
Pierotti Marco A.,
Porta Giuseppe Della,
Parmiani Giorgio
Publication year - 1991
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910470423
Subject(s) - mutation , microbiology and biotechnology , methylcholanthrene , biology , malignant transformation , fibrosarcoma , transplantation , carcinogenesis , gene , point mutation , transfection , carcinogen , dna , oligonucleotide , antigen , transformation (genetics) , cancer research , genetics , medicine , surgery
The DNA of 22 fibrosarcomas, newly induced in BALB/c mice by subcutaneous doses of 3‐methylcholanthrene (3‐MCA), was tested in NIH 3T3 transformation assay. Activation of K‐ ras and N‐ ras was found in 7 and 3 cases respectively. No H‐ ras activation was detected. Polymerase chain reaction and oligonucleotide hybridization performed on the DNA of the 22 sarcomas revealed 5 cases of K‐ ras mutation at codon 12, 3 at codon 13 and I at both codons. One case of K13 mutation was not detectable by transfection. Three cases of mutation at codon 61 of N‐ ras were also found, one of which was simultaneous with a K12 mutation. Tumor‐specific transplantation antigens (TSTA) were assessed in the 22 original tumors. Altogether 16 sarcomas were immunogenic, with the highest frequency of TSTA tumors (10/11 and 5/6) in the groups given 1.0 and 0.1 mg of 3‐MCA respectively, the lowest (1/5) in that with 0.01 mg of carcinogen; ras mutations occurred in the DNAs of 11 out of the 16 TSTA + sarcomas, but none of the DNAs of the 6 TSTA‐ tumors showed ras mutation. The results suggest that 3‐MCA‐induced transformation of subcutaneous fibroblasts can involve mutations in codons 12, 13 or 61 of K‐ and N‐ but not H‐ ras gene and that such mutation is accompanied by the expression of TSTA.