Horizontal transfer of oncogenes by uptake of apoptotic bodies
Horizontal transfer of oncogenes by uptake of apoptotic bodies
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DOI：
10.1073/pnas.101129998
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发表时间：
2001-05-22
影响因子：
11.1
通讯作者：
Holmgren, L
中科院分区：
文献类型：
--
作者：
Bergsmedh, A;Szeles, A;Holmgren, L
肿瘤形成涉及恶性生长所需的一系列遗传改变的积累。在大多数恶性肿瘤中，可以在染色体水平上观察到遗传变化，如整个或大部分染色体的丢失或获得。在这里，我们提供的证据表明，肿瘤DNA可能是通过摄取凋亡小体水平转移。来自H-ras（V12）和人c-myc转染大鼠成纤维细胞的凋亡小体的吞噬作用导致体外接触抑制的丧失和体内致瘤表型。荧光原位杂交分析显示受体鼠细胞核中存在大鼠染色体或大鼠和小鼠融合染色体。只要转移的DNA赋予细胞选择性优势，并且吞噬宿主细胞是p53阴性的，则转移的DNA被增殖。这些结果表明，真核细胞之间的DNA横向转移可能会导致非整倍体和肿瘤形成所必需的遗传变化的积累。
Tumor formation involves the accumulation of a series of genetic alterations that are required for malignant growth. In most malignancies, genetic changes can be observed at the chromosomal level as losses or gains of whole or large portions of chromosomes. Here we provide evidence that tumor DNA may be horizontally transferred by the uptake of apoptotic bodies. Phagocytosis of apoptotic bodies derived from H-ras(V12)- and human c-myc-transfected rat fibroblasts resulted in loss of contact inhibition in vitro and a tumorigenic phenotype in vivo. Fluorescence in site hybridization analysis revealed the presence of rat chromosomes or of rat and mouse fusion chromosomes in the nuclei of the recipient murine cells. The transferred DNA was propagated, provided that the transferred DNA conferred a selective advantage to the cell and that the phagocytotic host cell was p53-negative. These results suggest that lateral transfer of DNA between eukaryotic cells may result in aneuploidy and the accumulation of genetic changes that are necessary for tumor formation.