Stable overexpression of MEN1 suppresses tumorigenicity of RAS
Stable overexpression of MEN1 suppresses tumorigenicity of RAS
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DOI：
10.1038/sj.onc.1203005
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发表时间：
1999-10-21
期刊：
影响因子：
8
通讯作者：
Marx, SJ
中科院分区：
文献类型：
--
作者：
Kim, YS;Burns, AL;Marx, SJ
虽然有间接遗传学证据表明MEN 1（多发性内分泌瘤1型基因）是一种肿瘤抑制基因，但对MEN 1编码的蛋白质menin知之甚少。Menin在充分表征的鼠肿瘤细胞系（缬氨酸-12）-RAS转化的NTH 3 T3细胞中稳定过表达。Menin过表达使RAS转化的NIH 3 T3细胞的形态向野生型NIH 3 T3细胞的更扁平和更扩散的成纤维细胞形状恢复。RAS转化细胞在0.5%小牛血清中的增殖速率也随着menin过表达而减慢。Menin过表达可降低RAS诱导的软琼脂集落形成。Menin也减少了裸鼠注射细胞后的肿瘤生长。总之，MEN 1的稳定过表达在体外和体内部分抑制RAS介导的肿瘤表型。过表达的menin蛋白具有生物学效应，直接支持MEN 1基因作为肿瘤抑制因子的功能。
Although there is indirect genetic evidence that MEN1, the gene for multiple endocrine neoplasia type 1, is a tumor suppressor gene, little is known about the MEN1-encoded protein, menin. Menin was stably overexpressed in a well-characterized murine tumor cell line, (valine-12)-RAS-transformed NTH3T3 cells. Menin overexpression reverted the morphology of the RAS-transformed NIH3T3 cells towards the more flattened and more spread, fibroblastic shape of wild type NIH3T3 cells. The proliferation rate of the RAS-transformed cells in 0.5% calf serum was also slower with menin overexpression. Menin overexpression reduced the RAS-induced clonogenicity in soft agar. Menin also reduced tumor growth after injection of cells in nude mice. In conclusion, stable overexpression of MEN1 suppressed partially the RAS-mediated tumor phenotype in vitro and in vivo. Overexpressed menin protein had biological effects, directly supporting MEN1 gene function as a tumor suppressor.