Iwamoto Keisuke S, Barber Chad L
Roy E. Coats Research Laboratories, Department of Radiation Oncology, David Geffen School of Medicine at UCLA, University of California-Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA 90095, USA.
Mol Carcinog. 2007 Jul;46(7):497-502. doi: 10.1002/mc.20303.
The mannose 6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2r), a member of the IGF axis of growth factors, is a negative regulator of cell growth and a putative tumor suppressor gene. Regulation of M6P/IGF2r levels is critical in breast physiology; low expression is associated with various aspects of breast cancer. We have found that ionizing radiation induces the rapid expression of M6P/IGF2r in a dose-dependent manner in MCF7 human breast cancer cells. We show that this increase is mediated, at least in part, by a stabilization of M6P/IGF2r transcripts by radiation in both ER positive (MCF7 and T47D) and ER negative (MDA-MB-231) breast cancer cell lines. It is probable, therefore, that posttranscriptional dysregulation of M6P/IGF2r is a contributing mechanism in breast cancer development and breast cancer response to therapy. This is a novel find that underscores the importance of posttranscriptional control of radiation-induced gene expression-a phenomenon that has often been paradigmatically attributed to transcriptional control.
甘露糖6-磷酸/胰岛素样生长因子2受体（M6P/IGF2r）是生长因子IGF轴的成员之一，是细胞生长的负调节因子和一种假定的肿瘤抑制基因。M6P/IGF2r水平的调节在乳腺生理中至关重要；低表达与乳腺癌的各个方面相关。我们发现，电离辐射以剂量依赖的方式在MCF7人乳腺癌细胞中诱导M6P/IGF2r的快速表达。我们表明，这种增加至少部分是由辐射在雌激素受体阳性（MCF7和T47D）和雌激素受体阴性（MDA-MB-231）乳腺癌细胞系中稳定M6P/IGF2r转录本介导的。因此，M6P/IGF2r的转录后失调可能是乳腺癌发展和乳腺癌对治疗反应的一个促成机制。这是一项新发现，强调了辐射诱导基因表达的转录后控制的重要性——这一现象通常被范式性地归因于转录控制。
