Aberrant cAMP Metabolism in NF1 Malignant Peripheral Nerve Sheath Tumor Cells |
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Authors: | Ian Dang George H. De Vries |
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Affiliation: | (1) Research 151, Hines VA Hospital, Hines, IL 60141, USA;(2) Department of Cell Biology, Neurobiology and Anatomy, Loyola University Medical Center, Maywood, IL 60153, USA;(3) Research 151, McGuire VA Medical Center, 1201 Broad Rock Boulevard, Richmond, VA 23249, USA;(4) Department of Anatomy and Neurobiology, Medical College of Virginia Campus of Virginia Commonwealth University, Richmond, VA 23298-0709, USA |
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Abstract: | 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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