Steroid Hormones in NF1 Tumorigenesis
Final rept. 1 Aug 2001-31 Jul 2005
FLORIDA UNIV GAINESVILLE
Pagination or Media Count:
This work tested the hypothesis that human NF1 tumor Schwann cells have growth alterations in response to estrogen or progesterone. Specific Aim I measured steroid receptor expression in human normal, NF1 neurofibroma and MPNST Schwann cells. We found less than 2-fold difference in these transcripts in tumor versus normal Schwann cells in those that changed. immunohistochemistry for progesterone receptor was positive in subset of neurofibromas, consistent with transcript data in primary tumors. Specific Aim 2 tested in vitro response of tumor cells to hormones, and found several significant proliferation and apoptosis responses of the Schwann cell cultures to hormones or antagonists. Specific Aim 3 tested hormone response of tumor cells xenografted into mouse nerve. About half of xenografts showed a response to one or the other or both hormones in relative proliferation-to-apoptosis ratio. There was no correlation with tumor type or gender, so the cells behave heterogeneously some have tumor-like growth in response to a hormone, and some grew less than placebo. This supports the hypothesis that steroid hormones can significantly affect the growth of NF1 tumor cells.
- Medicine and Medical Research