Bcl-2与M-Myc共表达增加神经母细胞瘤细胞系中的胰岛素样生长因子1受体（IGF-IR）及恶性生长特征。
Bcl-2 and M-Myc coexpression increases IGF-IR and features of malignant growth in neuroblastoma cell lines.
作者信息
Jasty R, van Golen C, Lin H J, Solomon G, Heidelberger K, Polverini P, Opipari A, Feldman E, Castle V P
机构信息
Department of Pediatrics, Medical College of Ohio, Toledo, OH 43614, USA.
出版信息
Neoplasia. 2001 Jul-Aug;3(4):304-13. doi: 10.1038/sj.neo.7900171.
The bcl-2 and c-myc oncogenes cooperate to transform multiple cell types. In the pediatric malignancy NB(2), Bcl-2 is highly expressed. In tumors with a poor prognosis, N-Myc, a protein homologous to c-Myc, is overexpressed as a result of gene amplification. The present study was designed to determine whether Bcl-2 cooperates with N-Myc to bestow a tumorigenic phenotype to neuroblastoma (NB) cells. NB cell lines that at baseline express neither Bcl-2 nor N-Myc were stably transfected to express these gene products. In this model, we found Bcl-2 rescues N-Myc-expressing cells from apoptosis induced by serum withdrawal. Coexpression of Bcl-2 and N-Myc supports growth in low serum conditions and anchorage-independent growth in soft agar. Similarly, in vivo tumorigenic and angiogenic activity was dependent on coexpression. Our data further suggests that the mechanism underlying these changes involves the receptor for insulin growth factor type I (IGF-IR).
bcl-2和c-myc癌基因协同作用可使多种细胞类型发生转化。在儿童恶性肿瘤神经母细胞瘤（NB）中，Bcl-2高度表达。在预后不良的肿瘤中，与c-Myc同源的蛋白质N-Myc由于基因扩增而过度表达。本研究旨在确定Bcl-2是否与N-Myc协同作用，赋予神经母细胞瘤（NB）细胞致瘤表型。对在基线时既不表达Bcl-2也不表达N-Myc的NB细胞系进行稳定转染，以表达这些基因产物。在该模型中，我们发现Bcl-2可使表达N-Myc的细胞免于血清撤除诱导的凋亡。Bcl-2和N-Myc的共表达支持在低血清条件下的生长以及在软琼脂中的非锚定依赖性生长。同样，体内致瘤和血管生成活性也依赖于共表达。我们的数据进一步表明，这些变化的潜在机制涉及I型胰岛素生长因子受体（IGF-IR）。
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