A RETROVIRUS VECTOR EXPRESSING THE PUTATIVE MAMMARY ONCOGENE INT-1 CAUSES PARTIAL TRANSFORMATION OF A MAMMARY EPITHELIAL-CELL LINE
A RETROVIRUS VECTOR EXPRESSING THE PUTATIVE MAMMARY ONCOGENE INT-1 CAUSES PARTIAL TRANSFORMATION OF A MAMMARY EPITHELIAL-CELL LINE
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DOI：
10.1016/0092-8674(86)90699-9
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发表时间：
1986-09-26
期刊：
影响因子：
64.5
通讯作者：
VARMUS, HE
中科院分区：
文献类型：
--
作者：
BROWN, AMC;WILDIN, RS;VARMUS, HE
在由小鼠乳腺肿瘤病毒（MMTV）诱导的乳腺肿瘤中，int-1基因经常被相邻的前病毒插入激活，从而强烈地参与肿瘤发生。为了寻求int-1的直接生物学效应，以验证其作为致癌基因的作用，我们构建了含有该基因的逆转录病毒载体，并研究了其对组织培养细胞的影响。int-1在乳腺上皮细胞系中的表达引起了显著的形态学变化，在高细胞密度下不受限制的生长，以及在单层上形成病灶，尽管这些细胞在体内不会致瘤。这种由int-1诱导的部分转化在被基因中携带移码突变的其他相同病毒感染的细胞中未观察到。这些发现有力地支持了这一假设，即int-1在MMT诱导的乳腺肿瘤发生中起着功能性作用。
In mammary tumors induced by the mouse mammary tumor virus (MMTV), the int-1 gene is frequently activated by adjacent proviral insertions and is thereby strongly implicated in tumorigenesis. To seek a direct biological effect of int-1 that would validate its proposed role as an oncogene, we constructed a retrovirus vector containing the gene and examined its effects on tissue culture cells. Expression of int-1 in a mammary epithelial cell line caused striking morphological changes, unrestricted growth at high cell density, and focus formation on a monolayer, although the cells were not tumorigenic in vivo. This partial transformation induced by int-1 was not observed in cells infected by an otherwise identical virus bearing a frameshift mutation in the gene. These findings strongly support the hypothesis that int-1 plays a functional role in MMTV-induced mammary tumorigenesis.