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.
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.
Roth
Therese M
TM
Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, Michigan 48109-2200, USA.
Ramamurthy
Poornapriya
P
Muir
David
D
Wallace
Margaret R
MR
Zhu
Yuan
Y
Chang
Lou
L
Barald
Kate F
KF
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*
D017931:DNA Primers; D025542:Neurofibromin 1; D011959:Receptors, Estradiol; D004958:Estradiol; D000077584:2-Methoxyestradiol