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.
Iwamoto
Keisuke S
KS
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.
Barber
Chad L
CL
D015152:Blotting, Northern; D001943:Breast Neoplasms / Q000532:radiotherapy*; D004307:Dose-Response Relationship, Radiation; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000528:radiation effects*; D006801:Humans; D008360:Mannosephosphates / Q000235:genetics* / Q000378:metabolism; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000378:metabolism; D011839:Radiation, Ionizing; D017527:Receptor, IGF Type 2 / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000528:radiation effects*; D014407:Tumor Cells, Cultured / Q000378:metabolism / Q000528:radiation effects
D008360:Mannosephosphates; D012333:RNA, Messenger; D017527:Receptor, IGF Type 2; C027693:mannose-6-phosphate