Transforming gene in human atherosclerotic plaque DNA.
Transforming gene in human atherosclerotic plaque DNA.
复制标题
人类动脉粥样硬化斑块 DNA 中的转化基因。
DOI：
10.1073/pnas.83.20.7951
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发表时间：
1986
影响因子：
11.1
通讯作者：
Mindich,B
中科院分区：
文献类型：
--
作者：
Penn,A;Garte,SJ;Warren,L;Nesta,D;Mindich,B
单克隆假说将动脉粥样硬化斑块等同于良性平滑肌细胞肿瘤，并提出斑块可以通过突变或病毒事件产生。在这里，我们提供了直接的证据，分子事件，迄今为止只与肿瘤细胞，是共同的斑块细胞。三组不同的人冠状动脉斑块（hCAP）DNA样品转染到NIH 3 T3细胞中产生转化灶。来自一组正常非癌人体组织（包括冠状动脉）的DNA样本在检测中呈阴性。Southern印迹的焦点DNA产生阳性信号时，杂交到32 P标记的切口翻译的重复的人“Alu”DNA序列。来自克隆灶的DNA成功地用于第二轮转染。与切口翻译的v-Ki-ras、v-Ha-ras或N-ras探针杂交的焦点DNA未能检测到这些基因的人类片段。来自五个克隆中的每一个的原代病灶细胞在注射到裸鼠中后引发肿瘤（6/42）。BamHI消化的肿瘤DNA与Alu杂交后，检测到几条明显的高分子量（大于6.6个酶）条带。这些hCAP DNA相关肿瘤的初步特征表明，它们类似于注射ras转化细胞到裸鼠后出现的纤维肉瘤。我们提出，斑块细胞中的转化基因的行为方式类似于癌基因在癌细胞中的行为方式。
The monoclonal hypothesis equates atherosclerotic plaques with benign smooth muscle cell tumors and proposes that plaques can arise via mutational or viral events. Here, we provide direct evidence that molecular events, heretofore associated only with tumor cells, are common to plaque cells as well. Three distinct groups of human coronary artery plaque (hCAP) DNA samples transfected into NIH 3T3 cells gave rise to transformed foci. DNA samples from a panel of normal noncancerous human tissues, including coronary artery, were negative in the assay. Southern-blotted focus DNA yielded positive signals when hybridized to the 32P-labeled nick-translated repetitive human "Alu" DNA sequence. The DNA from cloned foci was used successfully in a second round of transfection. Focus DNA hybridized to nick-translated v-Ki-ras, v-Ha-ras, or N-ras probes failed to detect human fragments of these genes. Primary focus cells from each of five clones elicited tumors after injection into nude mice (6/42). Several distinct high molecular weight (greater than 6.6 kilobases) bands were detected after BamHI-digested tumor DNA was hybridized to Alu. Preliminary characterization of these hCAP DNA-associated tumors indicates that they are similar to the fibrosarcomas that arise after injection of ras-transformed cells into nude mice. We propose that transforming genes in plaque cells behave in a manner analogous to the way in which oncogenes behave in cancer cells.