A POSITION 12-ACTIVATED H-RAS ONCOGENE IN ALL HS578T MAMMARY CARCINOSARCOMA CELLS BUT NOT NORMAL MAMMARY CELLS OF THE SAME PATIENT
A POSITION 12-ACTIVATED H-RAS ONCOGENE IN ALL HS578T MAMMARY CARCINOSARCOMA CELLS BUT NOT NORMAL MAMMARY CELLS OF THE SAME PATIENT
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DOI：
10.1073/pnas.81.17.5384
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发表时间：
1984-01-01
期刊：
影响因子：
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通讯作者：
AARONSON, SA
中科院分区：
文献类型：
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作者：
KRAUS, MH;YUASA, Y;AARONSON, SA
在21例人乳腺肿瘤中，只有癌肉瘤细胞系HS 578 T的DNA呈阳性。在该细胞系中鉴定的Harvey（H）-ras癌基因以生物活性形式克隆，并且鉴定激活损伤为第12密码子中腺嘌呤对鸟嘌呤的单核苷酸取代。结果是在p21编码序列的这个位置上用Asp取代Gly。这种改变在H-ras原癌基因中产生Msp I/Hpa-II限制性位点多态性的知识使得有可能在正常细胞以及同一患者的克隆来源的肿瘤细胞系中调查活化的H-ras等位基因的存在。正常HS 578细胞中存在未改变的H-ras等位基因。相反，分析的每个克隆来源的HS 578 T肿瘤细胞系含有在位置12处具有遗传改变的H-ras癌基因。这些发现证实了该癌基因的激活是在所有HS 578 T肿瘤细胞中选择的体细胞事件的结果。
Among 21 human mammary tumors analyzed for transforming genes by transfection of NIH/3T3 cells, only DNA of a carcinosarcoma cell line, HS578T, registered as positive. A Harvey (H)-ras oncogene identified in this line was cloned in biologically active form and the activating lesion was identified as a single nucleotide substitution of adenine for guanine in the 12th codon. This results is substitution of Asp for Gly at this position of the p21 coding sequence. Knowledge that this alteration creates a restriction site polymorphism for Msp I/Hpa-II in the H-ras protooncogene made it possible to survey for the presence of the activated H-ras allele in normal cells as well as in clonally derived tumor cell lines of the same patient. Unaltered H-ras alleles are present in normal HS578 cells. In contrast, every clonally derived HS578T tumor cell line analyzed contained the H-ras oncogene possessing the genetic alteration at position 12. These findings establish that activation of this oncogene was the result of a somatic event selected within all HS578T tumor cells.