title: Influence of hormones and hormone metabolites on the growth of Schwann cells derived from embryonic stem cells and on tumor cell lines expressing variable levels of neurofibromin.
abstract: Loss of neurofibromin, the protein product of the tumor suppressor gene neurofibromatosis type 1 (NF1), is associated with neurofibromas, composed largely of Schwann cells. The number and size of neurofibromas in NF1 patients have been shown to increase during pregnancy. A mouse embryonic stem cell (mESC) model was used, in which mESCs with varying levels of neurofibromin were differentiated into Schwann-like cells. NF1 cell lines derived from a malignant and a benign human tumor were used to study proliferation in response to hormones. Estrogen and androgen receptors were not expressed or expressed at very low levels in the NF1+/+ cells, at low levels in NF1+/-cells, and robust levels in NF1-/-cells. A 17beta-estradiol (E2) metabolite, 2-methoxy estradiol (2ME2) is cytotoxic to the NF1-/- malignant tumor cell line, and inhibits proliferation in the other cell lines. 2ME2 or its derivatives could provide new treatment avenues for NF1 hormone-sensitive tumors at times of greatest hormonal influence.
authors.affiliation: Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, Michigan 48109-2200, USA.
authors.forename: Therese M
authors.initials: TM
authors.lastname: Roth
authors.forename: Poornapriya
authors.initials: P
authors.lastname: Ramamurthy
authors.forename: David
authors.initials: D
authors.lastname: Muir
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Wallace
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhu
authors.forename: Lou
authors.initials: L
authors.lastname: Chang
authors.forename: Kate F
authors.initials: KF
authors.lastname: Barald
mesh_terms: D000077584:2-Methoxyestradiol; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D017931:DNA Primers / Q000235:genetics; D053595:Embryonic Stem Cells / Q000166:cytology / Q000502:physiology*; D004958:Estradiol / Q000031:analogs & derivatives* / Q000633:toxicity; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D051379:Mice; D009455:Neurofibroma / Q000378:metabolism / Q000503:physiopathology*; D025542:Neurofibromin 1 / Q000235:genetics / Q000378:metabolism*; D011959:Receptors, Estradiol / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012583:Schwann Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*
chemical_list: D017931:DNA Primers; D025542:Neurofibromin 1; D011959:Receptors, Estradiol; D004958:Estradiol; D000077584:2-Methoxyestradiol