Schwann cells from human neurofibromas show increased proliferation rates under the influence of progesterone.
Neurofibromatosis type 1 (NF1) is a hereditary disease caused by mutations of the NF1 gene at 17q11.2. Loss of the NF1 gene product in Schwann cells leads to the development of benign nerve sheath tumors. These neurofibromas may occur at any time but tend to arise during periods of hormonal imbalance, suggesting that hormones influence neurofibroma growth. As steroid hormone levels rise during these times, we hypothesized that progesterone has proliferative effects on neurofibroma-derived Schwann cells. We chose specific medium conditions for selective proliferation of NF (+/-) and NF (-/-) cells from human neurofibromas. Genetic characterization was not performed, but former works have shown that under the conditions used (+/-) and (-/-) cells can be selected. Different progesterone concentrations were added at different days with BrdU-staining was performed to investigate proliferation rates and DAB-staining to identify a progesterone receptor. We could demonstrate that Schwann cells from human neurofibromas express progesterone receptors. These cells show elevated proliferation rates (highest in NF(-/-) cells) under progesterone, whereas normal human Schwann cells were not affected. These data suggest that progesterone plays an important role in the development of neurofibromas in NF1.
Overdiek
Anja
A
Department of General Pediatrics, University Children's Hospital Duesseldorf, D-40225 Duesseldorf, Germany. a.overdiek@web.de
Winner
Ursula
U
Mayatepek
Ertan
E
Rosenbaum
Thorsten
T
D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D016514:Genes, Neurofibromatosis 1; D006801:Humans; D009456:Neurofibromatosis 1 / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D011374:Progesterone / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism*; D012583:Schwann Cells / Q000378:metabolism / Q000473:pathology*; D013997:Time Factors; D014407:Tumor Cells, Cultured
D011980:Receptors, Progesterone; D011374:Progesterone