Valentinis B, Morrione A, Peruzzi F, Prisco M, Reiss K, Baserga R
Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Oncogene. 1999 Mar 11;18(10):1827-36. doi: 10.1038/sj.onc.1202471.
The type 1 insulin-like growth factor receptor (IGF-IR) is known to protect cells from a variety of apoptotic injuries. In several instances, the anti-apoptotic effect of the wild type IGF-IR is more evident under conditions of anchorage-independence than in cells in monolayer cultures. We have investigated IGF-IR signaling in cells in anoikis, a form of apoptosis that occurs when cells are denied attachment to the extra-cellular matrix. IGF-I protects mouse embryo fibroblasts (MEF) from anoikis caused by withdrawal of growth factors. Survival is dependent on the concentration of IGF-I and a sufficient number of functional IGF-I receptors. In this model, IGF-I protection correlates best with ras activation and cell-to-cell aggregation, while PI3-kinase, Akt and MAP kinases seem to play a lesser, alternative role.
已知1型胰岛素样生长因子受体（IGF-IR）可保护细胞免受多种凋亡性损伤。在若干情况下，野生型IGF-IR的抗凋亡作用在非锚定依赖性条件下比在单层培养的细胞中更为明显。我们研究了细胞在失巢凋亡（anoikis）中的IGF-IR信号传导，失巢凋亡是一种当细胞失去与细胞外基质的附着时发生的凋亡形式。IGF-I可保护小鼠胚胎成纤维细胞（MEF）免受因生长因子撤除导致的失巢凋亡。细胞存活取决于IGF-I的浓度和足够数量的功能性IGF-I受体。在该模型中，IGF-I的保护作用与ras激活和细胞间聚集最为相关，而PI3激酶、Akt和丝裂原活化蛋白激酶（MAP激酶）似乎起较小的替代作用。
