title: In vitro studies of steroid hormones in neurofibromatosis 1 tumors and Schwann cells.
abstract: The most common NF1 feature is the benign neurofibroma, which consists predominantly of Schwann cells. Dermal neurofibromas usually arise during puberty and increase in number throughout adulthood. Plexiform neurofibromas, associated with larger nerves, are often congenital and can be life threatening. Malignant peripheral nerve sheath tumors (MPNST) in NF1 are believed to arise from plexiforms in 5%-10% of patients. There are reports of increased potential for malignant transformation of plexiform tumors and increase in dermal neurofibromas, during pregnancy. These observations suggest that steroid hormones influence neurofibroma growth, and our work is the first to examine steroid hormone receptor expression and ligand-mediated cell growth and survival in normal human Schwann cells and neurofibroma-derived Schwann cell cultures. Immunohistochemistry and real-time PCR showed that estrogen receptors (ERs), progesterone receptor (PR), and androgen receptor are differentially expressed in primary neurofibromas and in NF1 tumor-derived Schwann cell cultures compared to normal Schwann cells. However, there is substantial heterogeneity, with no clear divisions based on tumor type or gender. The in vitro effects of steroid hormone receptor ligands on proliferation and apoptosis of early passage NF1 tumor-derived Schwann cell cultures were compared to normal Schwann cell cultures. Some statistically significant changes in proliferation and apoptosis were found, also showing heterogeneity across groups and ligands. Overall, the changes are consistent with increased cell accumulation. Our data suggest that steroid hormones can directly influence neurofibroma initiation or progression by acting through their cognate receptor, but that these effects may only apply to a subset of tumors, in either gender.
authors: Department of Molecular Genetics and Microbiology, UF College of Medicine, University of Florida, Gainesville, FL 32610, USA.
authors: Lauren
authors: L
authors: Fishbein
authors: Xuelian
authors: X
authors: Zhang
authors: Lori B
authors: LB
authors: Fisher
authors: Hua
authors: H
authors: Li
authors: Martha
authors: M
authors: Campbell-Thompson
authors: Anthony
authors: A
authors: Yachnis
authors: Allan
authors: A
authors: Rubenstein
authors: David
authors: D
authors: Muir
authors: Margaret R
authors: MR
authors: Wallace
mesh_terms: D017209:Apoptosis; D049109:Cell Proliferation; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D007124:Immunoenzyme Techniques; D020287:In Situ Nick-End Labeling; D066298:In Vitro Techniques; D008297:Male; D009456:Neurofibromatosis 1 / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism; D011987:Receptors, Steroid / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012583:Schwann Cells / Q000378:metabolism* / Q000473:pathology
chemical_list: D066246:ErbB Receptors; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D011987:Receptors, Steroid; D040262:Receptors, Vascular Endothelial Growth Factor