Campo M S, McCaffery R E, Doherty I, Kennedy I M, Jarrett W F
Beatson Institute for Cancer Research, Bearsden, Glasgow, UK.
Oncogene. 1990 Mar;5(3):303-8.
The possible activation of ras sequences in papillomavirus-associated carcinomas of the upper alimentary canal of cattle was investigated by restriction enzyme and hybridization analysis, and by DNA-mediated transformation of NIH3T3 cells. In three cancers, a squamous cell carcinoma of the palate, a squamous cell carcinoma of the rumen, and a transitional cell carcinoma of the urinary bladder, repetitive DNA sequences present in the Ha-ras 1 locus showed anomalous restriction patterns, indicating rearrangements and, in the case of the palate cancer, amplification. Genomic DNA from several cancers was capable of inducing focus formation in the NIH3T3 transformation test. DNA from primary, secondary and tertiary transformants was analysed by hybridization to bovine ras probes and by nucleotide sequencing of polymerase chain reaction products. Bovine Ha-ras 1 sequences were found in all transformants, but no nucleotide differences were detected in exon 1 or exon 2 between normal, cancer and transformed cells. It is concluded that the Ha-ras 1 gene is activated in alimentary canal carcinomas, although the activating mutation has not yet been mapped. The possible relationship between papillomavirus infection and activation of the ras gene is considered.
通过限制性内切酶和杂交分析以及DNA介导的NIH3T3细胞转化，对牛上消化道乳头瘤病毒相关癌中ras序列的可能激活情况进行了研究。在三种癌症中，即腭部鳞状细胞癌、瘤胃鳞状细胞癌和膀胱移行细胞癌，Ha-ras 1基因座中存在的重复DNA序列显示出异常的限制性图谱，表明发生了重排，在腭部癌中还存在扩增。几种癌症的基因组DNA能够在NIH3T3转化试验中诱导灶形成。通过与牛ras探针杂交以及对聚合酶链反应产物进行核苷酸测序，对一级、二级和三级转化体的DNA进行了分析。在所有转化体中均发现了牛Ha-ras 1序列，但在正常细胞、癌细胞和转化细胞之间，外显子1或外显子2中未检测到核苷酸差异。得出的结论是，Ha-ras 1基因在消化道癌中被激活，尽管激活突变尚未定位。同时还考虑了乳头瘤病毒感染与ras基因激活之间的可能关系。
