Transformation of murine fibroblasts by a retrovirus encoding the murine c-fms proto-oncogene.
Transformation of murine fibroblasts by a retrovirus encoding the murine c-fms proto-oncogene.
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发表时间：
1989-08
期刊：
影响因子：
8
通讯作者：
L. Rohrschneider;V. Rothwell;N. Nicola
中科院分区：
文献类型：
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作者：
L. Rohrschneider;V. Rothwell;N. Nicola
c-fms原癌基因是巨噬细胞集落刺激因子M-CSF的生长因子受体。在本文中，我们研究了c-fms在一个物种中的不适当表达，作为分析c-fms促进转化、生长和分化活性的相关模型。构建逆转录病毒载体用于在鼠细胞中表达鼠c-fms原癌基因。在成纤维细胞中进行该载体的初始表征。用鼠c-fms逆转录病毒感染Balb/c 3 T3细胞，导致细胞表面gp 140 c-fms前体和gp 165 c-fms成熟受体蛋白的高水平表达，并且这两种蛋白都表现出激酶活性。每个细胞可检测到高达3.3 × 10（4）个M-CSF受体。c-fms逆转录病毒诱导的形态学转化的Balb/c细胞，表现出锚定独立的软琼脂中的生长，并在同系动物中产生逐渐生长的肿瘤的病灶。Balb/c细胞合成并分泌M-CSF，因此这些结果表明，仅由不适当的内源性M-CSF产生细胞中正常生长因子受体的表达引起的自分泌转化机制。
The c-fms proto-oncogene is the growth factor receptor for the macrophage colony stimulating factor, M-CSF. In this paper we have investigated the inappropriate expression of c-fms within a species as a relevant model for analysing transformation, growth, and differentiation promoting activities of c-fms. A retroviral vector was constructed for the expression of the murine c-fms proto-oncogene in murine cells. Initial characterization of this vector was performed in fibroblasts. Infection of Balb/c 3T3 cells with the murine c-fms retrovirus resulted in high level expression of the gp140c-fms precursor and the gp165c-fms mature receptor protein on the cell surface and both proteins exhibited kinase activity. Up to 3.3 x 10(4) M-CSF receptors per cell were detectable. The c-fms retrovirus induced foci of morphologically transformed Balb/c cells that exhibited anchorage independent growth in soft agar and produced progressively growing tumors in syngeneic animals. The Balb/c cells synthesize and secrete M-CSF and therefore these results suggest an autocrine mechanism of transformation caused solely by the expression of a normal growth factor receptor in an inappropriate, endogenous M-CSF-producing cell.