Journal
NEUROCHEMICAL RESEARCH
Volume 36, Issue 9, Pages 1697-1705Publisher
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s11064-011-0433-2
Keywords
cAMP; Neurofibromatosis type I; Schwann cells; MPNST cell lines; Normal human Schwann cells; Prostaglandin metabolism
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Funding
- US Army Medical Research and Material Command [DAMD17-98-8607]
- Department of Veterans Affairs
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Malignant peripheral nerve sheath (MPNST) cell lines derived from patients with neurofibromatosis type 1 (NF!) were found to have basal cAMP levels which are two-fold higher than cAMP levels in normal human adult Schwann cells (nHSC). PCR analysis also revealed that normal adult human Schwann cells express mRNA for types Ill, IV, and IX adenylyl cyclase (AC) while NF1 MPNST cells express AC mRNA of types II, V, and VIII in addition to expressing all the isoforms of normal adult human Schwann cells. Further PCR analysis revealed that NF1 MPNST lines express mRNA for EP2 and EP4 prostaglandin receptors whereas nHSC only express mRNA for the EP2 receptor. Exogenous prostaglandins alone or in combination with PDGF BB induced greater increases in cAMP levels and proliferation of NF1 MPNST cells compared to nHSC. We conclude that aberrant cAMP signaling in NF1 MPNST cells contributes to tumor formation in NF1 patients.
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