Seeding and propagation of untransformed mouse mammary cells in the lung.

Seeding and propagation of untransformed mouse mammary cells in the lung.
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DOI:
10.1126/science.1161621
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发表时间:
2008-09-26
期刊:
Science (New York, N.Y.)
影响因子:
--
通讯作者:
Varmus H
Varmus H
中科院分区:
其他
文献类型:
--
作者:
Podsypanina K;Du YC;Jechlinger M;Beverly LJ;Hambardzumyan D;Varmus H

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肿瘤细胞获得转移能力被认为是恶性肿瘤演变的晚期事件。我们报告说,未转化的小鼠乳腺细胞,已被设计为表达诱导致癌转基因MYC和KrasD12,或多瘤中间T,并引入到小鼠的体循环可以绕过转化的主要网站和发展成转移性肺病变后,立即或延迟致癌基因诱导。因此,以前未转化的乳腺细胞一旦进入血液就可能在肺部定居,并可能在癌基因激活后呈恶性生长。缺乏致癌转基因的乳腺细胞显示出类似的长期驻留在肺中的能力,但不形成异位肿瘤。
The acquisition of metastatic ability by tumor cells is considered a late event in the evolution of malignant tumors. We report that untransformed mouse mammary cells that have been engineered to express the inducible oncogenic transgenes MYC and KrasD12, or polyoma middle T, and introduced into the systemic circulation of a mouse can bypass transformation at the primary site and develop into metastatic pulmonary lesions upon immediate or delayed oncogene induction. Therefore, previously untransformed mammary cells may establish residence in the lung once they have entered the bloodstream and may assume malignant growth upon oncogene activation. Mammary cells lacking oncogenic transgenes displayed a similar capacity for long-term residence in the lungs but did not form ectopic tumors.
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