Wang W, Kumar P, Wang W, Epstein J, Helman L, Moore J V, Kumar S
Manchester Metropolitan University, Manchester, United Kingdom.
Cancer Res. 1998 Oct 1;58(19):4426-33.
The mouse myoblast C2C12 cell line transfected singly with cDNA for Pax-3, PAX3-FKHR, or insulin-like growth factor (IGF) II or cotransfected with IGF-II plus Pax-3 or with IGF-II plus PAX3-FKHR genes showed an altered morphology, a lack of differentiation, and higher proliferation rates in vitro. On s.c. injection into nude mice, tumors grew from transfected cell lines but not from cells transfected with the empty vector. Tumors derived from IGF-II/PAX3-FKHR- and IGF-II-transfected cells grew most rapidly. Cotransfection of IGF-II plus Pax-3 induced tumors comprised highly differentiated striated muscle cells; Pax-3, PAX3-FKHR, or IGF-II transfection produced tumors at varying stages of differentiation. Tumors derived from IGF-II plus PAX3-FKHR-cotransfected cells were composed of undifferentiated cells. This was the only tumor type to infiltrate the underlying muscle. The most angiogenesis and the least apoptosis were observed in the latter tumors. These results support the hypothesis that PAX3-FKHR interacts with IGF-II to play a critical role in the oncogenesis of rhabdomyosarcoma.
单独用编码Pax-3、PAX3-FKHR或胰岛素样生长因子（IGF）II的cDNA转染，或用IGF-II与Pax-3共转染，或用IGF-II与PAX3-FKHR基因共转染的小鼠成肌细胞C2C12细胞系，在体外表现出形态改变、缺乏分化以及更高的增殖率。将其皮下注射到裸鼠体内后，转染细胞系可形成肿瘤，而用空载体转染的细胞则不能形成肿瘤。源自IGF-II/PAX3-FKHR和IGF-II转染细胞的肿瘤生长最为迅速。IGF-II与Pax-3共转染诱导形成的肿瘤包含高度分化的横纹肌细胞；Pax-3、PAX3-FKHR或IGF-II转染产生的肿瘤处于不同的分化阶段。源自IGF-II与PAX3-FKHR共转染细胞的肿瘤由未分化细胞组成。这是唯一浸润下层肌肉的肿瘤类型。在后者的肿瘤中观察到最多的血管生成和最少的细胞凋亡。这些结果支持了PAX3-FKHR与IGF-II相互作用在横纹肌肉瘤肿瘤发生中起关键作用的假说。
