Selection of early-occurring mutations dictates hormone-independent prouession in mouse mammary tumor lines
Selection of early-occurring mutations dictates hormone-independent prouession in mouse mammary tumor lines
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DOI：
10.1128/jvi.00234-06
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发表时间：
2006-11-01
影响因子：
5.4
通讯作者：
Kordon, Edith C.
中科院分区：
文献类型：
--
作者：
Gattelli, Albana;Zimberlin, Marfa N.;Kordon, Edith C.
携带三种小鼠乳腺肿瘤病毒（MMTV）变种的小鼠会形成妊娠依赖性（PD）肿瘤，并通过连续传代进展为妊娠非依赖性（PI）行为。在此，我们从 8 个独立的肿瘤系中鉴定出 PI 移植物中的 10 个主要插入。这些突变也在早期 PD 传代的小细胞群中检测到。此外，我们在基因 Rspo3 的上游发现了一个新的病毒插入，该基因在八个独立肿瘤系中的三个中过表达，并编码与最近描述的由 Int7 编码的蛋白质非常相似的蛋白质。这项研究表明，在激素独立的过程中，具有特定突变的细胞的克隆扩张可能比新 MMTV 插入的发生更相关。
Mice harboring three mouse mammary tumor virus (MMTV) variants develop pregnancy-dependent (PD) tumors that progress to pregnancy-independent (PI) behavior through successive passages. Herein, we identified 10 predominant insertions in PI transplants from 8 independent tumor lines. These mutations were also detected in small cell populations in the early PD passages. In addition, we identified a new viral insertion upstream of the gene Rspo3, which is overexpressed in three of the eight independent tumor lines and codes for a protein very similar to the recently described protein encoded by Int7. This study suggests that during progression towards hormone independence, clonal expansion of cells with specific mutations might be more relevant than the occurrence of new MMTV insertions.