Mammary tumor development in MMTV-c-myc/MMTV-v-Ha-ras transgenic mice is unaffected by osteopontin deficiency
Mammary tumor development in MMTV-c-myc/MMTV-v-Ha-ras transgenic mice is unaffected by osteopontin deficiency
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DOI：
10.1023/a:1006466516192
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发表时间：
2000-09-01
影响因子：
3.8
通讯作者：
Rittling, SR
中科院分区：
文献类型：
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作者：
Feng, F;Rittling, SR
在乳腺特异性启动子MMTV的控制下，在乳腺中特异性表达c-myc和v-Ha-ras的转基因小鼠在约46天的半衰期内发生单灶性乳腺肿瘤，并且这些肿瘤表达高水平的骨桥蛋白mRNA和蛋白。为了评估这些肿瘤对骨桥蛋白表达的需求，我们将表达这两种癌基因的转基因小鼠与靶向破坏骨桥蛋白基因的小鼠杂交。对同时表达myc和ras基因的野生型或破坏的OPN等位基因的同窝仔进行肿瘤发生率和生长率的评价。发现这两个参数都不受整个动物中缺乏骨桥蛋白的影响。Ras和myc的表达水平，在mRNA水平上测量，在两种基因型的肿瘤中没有差异。巨噬细胞积聚，虽然在不同的肿瘤之间变化很大，但与动物的OPN状态无关。相关基因BSP的表达在任何肿瘤中都没有检测到，并且在野生型和OPN -/-小鼠的骨骼中相似。类似地，玻连蛋白基因在任一基因型的肿瘤中以非常低的水平表达。这些结果表明，尽管OPN的表达水平很高，但它不是该系统中乳腺原发性肿瘤形成和生长所必需的，或者在完全缺乏骨桥蛋白的小鼠中可以被BSP和玻连蛋白以外的分子取代。
Transgenic mice expressing c-myc and v-Ha-ras specifically in the mammary gland under the control of the mammary specific promoter MMTV develop unifocal mammary tumors with a half time of about 46 days, and these tumors express high levels of osteopontin mRNA and protein. In order to evaluate the requirement for osteopontin expression by these tumors, we have crossed transgenic mice expressing these two oncogenes with mice with a targeted disruption of the osteopontin gene. Littermates expressing both myc and ras, and with either wild-type or disrupted OPN alleles were evaluated for tumor incidence and growth rate. Both of these parameters were found to be unaffected by a lack of osteopontin in the whole animal. Ras and myc expression level, measured at the level of mRNA, was not different in tumors of the two genotypes. Macrophage accumulation, while extremely variable among different tumors, did not correlate with the OPN status of the animals. Expression of the related gene BSP was not detected in any of the tumors, and was similar in bones of wildtype and OPN -/- mice. Similarly, the vitronectin gene was expressed at very low levels in tumors of either genotype. These results indicate that despite its high level of expression, OPN is either not required for mammary primary tumor formation and growth in this system, or can be replaced by molecules other than BSP and vitronectin in mice that totally lack osteopontin.