Reprogramming of a melanoma genome by nuclear transplantation
Reprogramming of a melanoma genome by nuclear transplantation
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DOI：
10.1101/gad.1213504
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发表时间：
2004-08-01
影响因子：
10.5
通讯作者：
Jaenisch, R
中科院分区：
文献类型：
--
作者：
Hochedlinger, K;Blelloch, R;Jaenisch, R
我们使用核移植来测试卵母细胞的重编程活性是否可以重建恶性癌细胞的发育多能性。我们在此表明，白血病、淋巴瘤和乳腺癌细胞的细胞核可以支持正常的植入前发育到囊胚阶段，但不能产生胚胎干细胞（ES）细胞。然而，从ras诱导的黑色素瘤细胞核中克隆的囊胚产生了胚胎干细胞，这些细胞有可能在体内分化为多种细胞类型，包括黑色素细胞、淋巴细胞和成纤维细胞。与供体小鼠模型相比，这些胚胎干细胞产生的嵌合体具有更高的外显率、更短的潜伏期和更广泛的肿瘤谱。这些结果表明，黑色素瘤细胞核的继发性变化与广泛的发育潜力是相容的，但在RAS的再激活下，小鼠易患黑色素瘤和其他恶性肿瘤。我们的发现为在整个动物的背景下研究给定癌症基因组的致瘤作用提供了范例。
We have used nuclear transplantation to test whether the reprogramming activity of oocytes can reestablish developmental pluripotency of malignant cancer cells. We show here that the nuclei of leukemia, lymphoma, and breast cancer cells could support normal preimplantation development to the blastocyst stage but failed to produce embryonic stem (ES) cells. However, a blastocyst cloned from a RAS-inducible melanoma nucleus gave rise to ES cells with the potential to differentiate into multiple cell types in vivo including melanocytes, lymphocytes, and fibroblasts. Chimeras produced from these ES cells developed cancer with higher penetrance, shorter latency, and an expanded tumor spectrum when compared with the donor mouse model. These results demonstrate that the secondary changes of a melanoma nucleus are compatible with a broad developmental potential but predispose mice to melanomas and other malignant tumors on reactivation of RAS. Our findings serve as a paradigm for studying the tumorigenic effect of a given cancer genome in the context of a whole animal.