• Schwann cells;
  • mouse ES cells;
  • pregnancy hormones;
  • steroid receptors


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 17β-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 greatet hormonal influence. Developmental Dynamics 237:513–524, 2008. © 2008 Wiley-Liss, Inc.