Prisco M, Romano G, Peruzzi F, Valentinis B, Baserga R
Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA.
Horm Metab Res. 1999 Feb-Mar;31(2-3):80-9. doi: 10.1055/s-2007-978703.
R-cells are mouse embryo fibroblasts with a targeted disruption of the insulin-like growth factor I receptor (IGF-IR) genes. Because R-cells do not express the IGF-IR, they are ideal for studying the biological effects of the insulin receptor (IR), independently from any contribution by the IGF-IR. By stably transfecting R-cells with constructs expressing the IR, we show here the IR can protect cells from apoptosis induced by anoikis or by okadaic acid. The IR, however, is not as efficient as the IGF-IR in protecting mouse embryo fibroblasts from apoptosis, even when IRS-1, one of its major substrates, is over-expressed. In addition, the protection by the IGF-IR is resistant to inhibitors of phosphatidylinositol 3-kinase (PI 3-ki), while the anti-apoptotic effect of the IR is sensitive. These experiments suggest that the IGF-IR uses an alternative anti-apoptotic pathway, not shared with the IR, which is PI3-ki-independent.
R细胞是胰岛素样生长因子I受体（IGF-IR）基因发生靶向破坏的小鼠胚胎成纤维细胞。由于R细胞不表达IGF-IR，因此它们是独立于IGF-IR的任何作用来研究胰岛素受体（IR）生物学效应的理想选择。通过用表达IR的构建体稳定转染R细胞，我们在此表明IR可以保护细胞免受失巢凋亡或冈田酸诱导的凋亡。然而，即使IR的主要底物之一IRS-1过表达，IR在保护小鼠胚胎成纤维细胞免受凋亡方面也不如IGF-IR有效。此外，IGF-IR的保护作用对磷脂酰肌醇3激酶（PI 3-ki）抑制剂具有抗性，而IR的抗凋亡作用则敏感。这些实验表明，IGF-IR使用一种不与IR共享的替代抗凋亡途径，该途径不依赖于PI3-ki。
