Radiation‐induced posttranscriptional control of M6P/IGF2r expression in breast cancer cell lines

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. © 2007 Wiley‐Liss, Inc.