The Cyclic AMP Pathway Is a Sex-Specific Modifier of Glioma Risk in Type I Neurofibromatosis Patients
| Autor: | Karlyne M. Reilly, Jingqin Luo, Anne C. Albers, David A. Stevenson, Douglas R. Stewart, David H. Gutmann, Uri Tabori, Debra Spoljaric, Tao Sun, David Viskochil, Joshua D. Schiffman, Michael Fisher, Robert C. McKinstry, Nicole M. Warrington, Jason T. Forys, Amanda Merkelson, Patricia C. Parkin, Sara Ganzhorn, Joshua B. Rubin, Jeffrey C. Allen, Todd E. Druley |
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| Rok vydání: | 2015 |
| Předmět: |
Male
Cancer Research Neurofibromatosis 1 Adenylate kinase Biology Cyclase Article Mice Sex Factors Risk Factors Glioma Cyclic AMP medicine Animals Humans Neurofibromatosis neoplasms Gene medicine.disease Sex specific nervous system diseases Mice Inbred C57BL Oncology Astrocytes Genetically Engineered Mouse Immunology Cancer research Female Signal transduction Signal Transduction |
| Zdroj: | Cancer Research. 75:16-21 |
| ISSN: | 1538-7445 0008-5472 |
| Popis: | Identifying modifiers of glioma risk in patients with type I neurofibromatosis (NF1) could help support personalized tumor surveillance, advance understanding of gliomagenesis, and potentially identify novel therapeutic targets. Here, we report genetic polymorphisms in the human adenylate cyclase gene adenylate cyclase 8 (ADCY8) that correlate with glioma risk in NF1 in a sex-specific manner, elevating risk in females while reducing risk in males. This finding extends earlier evidence of a role for cAMP in gliomagenesis based on results in a genetically engineered mouse model (Nf1 GEM). Thus, sexually dimorphic cAMP signaling might render males and females differentially sensitive to variation in cAMP levels. Using male and female Nf1 GEM, we found significant sex differences exist in cAMP regulation and in the growth-promoting effects of cAMP suppression. Overall, our results establish a sex-specific role for cAMP regulation in human gliomagenesis, specifically identifying ADCY8 as a modifier of glioma risk in NF1. Cancer Res; 75(1); 16–21. ©2014 AACR. |
| Databáze: | OpenAIRE |
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