ACTIVATION OF RAS ONCOGENES AND EXPRESSION OF TUMOR-SPECIFIC TRANSPLANTATION ANTIGENS IN METHYLCHOLANTHRENE-INDUCED MURINE FIBROSARCOMAS
ACTIVATION OF RAS ONCOGENES AND EXPRESSION OF TUMOR-SPECIFIC TRANSPLANTATION ANTIGENS IN METHYLCHOLANTHRENE-INDUCED MURINE FIBROSARCOMAS
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DOI：
10.1002/ijc.2910470423
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发表时间：
1991-02-20
影响因子：
6.4
通讯作者：
PARMIANI, G
中科院分区：
文献类型：
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作者：
CARBONE, G;BORRELLO, MG;PARMIANI, G
用NIH 3 T3转化试验检测了22例BALB/c小鼠皮下注射3-甲基胆蒽（3-MCA）诱发的纤维肉瘤的DNA。K-ras和N-ras的激活分别为7例和3例。未检测到H-ras激活。对22例肉瘤的DNA进行聚合酶链反应和寡核苷酸杂交，发现5例K-ras在第12密码子突变，3例在第13密码子突变，1例在两个密码子突变。1例K13突变未被转染检测到。3例N-ras基因第61位密码子突变，其中1例同时发生K12突变。在22个原始肿瘤中评估肿瘤特异性移植抗原（TSTA）。共有16例肉瘤具有免疫原性，其中TSTA+肿瘤的频率最高3-MCA 1.0和0.1mg组分别为10/11和5/6，以0.01mg组最低（1/5）; 16例TSTA+肉瘤中有11例发生ras基因突变，6例TSTA-肿瘤中无ras基因突变。结果提示，3-MCA诱导的皮下成纤维细胞转化可能涉及K-和N-ras基因密码子12、13或61的突变，而H-ras基因密码子12、13或61的突变并伴随着TSTA的表达。
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 1 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.