OVEREXPRESSION OF THE HUMAN INSULINLIKE GROWTH FACTOR-I RECEPTOR PROMOTES LIGAND-DEPENDENT NEOPLASTIC TRANSFORMATION
OVEREXPRESSION OF THE HUMAN INSULINLIKE GROWTH FACTOR-I RECEPTOR PROMOTES LIGAND-DEPENDENT NEOPLASTIC TRANSFORMATION
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DOI：
10.1128/mcb.10.2.464
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发表时间：
1990-02-01
影响因子：
5.3
通讯作者：
MILLER, AD
中科院分区：
文献类型：
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作者：
KALEKO, M;RUTTER, WJ;MILLER, AD
人胰岛素样生长因子I受体在NIH3T3细胞以及人和大鼠原代成纤维细胞株中过表达。NIH3T3细胞表现为高度转化的配体依赖表型。当暴露于胰岛素样生长因子I或超生理水平的胰岛素时，表达高水平受体的NIH 3T3细胞在组织培养皿中形成聚集体，在软琼脂中形成集落，并在裸鼠体内形成肿瘤。每个细胞表达100万个受体，是基线水平的40倍，这是非锚定生长所必需的。表达高水平受体的原代成纤维细胞在形态上表现出配体依赖性的变化，饱和密度增加，但没有获得完全转化的表型。结果表明，当扩增时，这种普遍存在的生长因子受体的行为类似于致癌蛋白，并能够促进体内肿瘤的生长。
The human insulinlike growth factor I receptor was overexpressed in NIH 3T3 cells as well as human and rat primary fibroblast strains. The NIH 3T3 cells displayed a ligand-dependent, highly transformed phenotype. When exposed to insulinlike growth factor I or supraphysiologic levels of insulin, NIH 3T3 cells that expressed high levels of receptors formed aggregates in tissue culture dishes, colonies in soft agar, and tumors in nude mice. Expression of 1 million receptors per cell, a 40-fold increase above the base-line level, was required for anchorage-independent growth. Primary fibroblasts that expressed high levels of receptors displayed a ligand-dependent change in morphology and an increase in saturation density but did not acquire a fully transformed phenotype. The results demonstrate that when amplified, this ubiquitous growth factor receptor behaves like an oncogenic protein and is capable of promoting neoplastic growth in vivo.