Neurofibromatosis type I (NF1), a common dominant condition, is characterized by abnormal proliferation of neural crest derived cells, including Schwann cells (thought to be the clonal element) in neurofibromas. The current therapy for neurofibromas is surgery, which is usually insufficient. Neurofibromas are often aggravated during puberty and pregnancy, suggesting an altered sensitivity to steroid hormones. NF1 patients and their physicians worry about this possible correlation when faced with decisions about hormone therapies for birth control, menopause, or disease treatments. To investigate this hypothesis, the type, relative quantity and localization of hormone receptors present in NF1 tumor Schwann cell cultures compared to normal Schwann cells will be measured through RT-PCR/Western blot and immunofluorescence, respectively. To investigate the functional role of these receptors, the tumor cultures will be assayed for increased proliferation and/or survival in response to these hormones. Expression of genes believed to be downstream targets of steroid hormones will also be analyzed. These studies will characterize the role of hormones in neurofibroma development, allowing for more educated medical decisions, as well as identifying potential targets for inhibiting tumor development.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Individual Predoctoral NRSA for M.D./Ph.D. Fellowships (ADAMHA) (F30)
Project #
5F30NS043951-02
Application #
6626107
Study Section
Special Emphasis Panel (ZRG1-F09 (20))
Program Officer
Finkelstein, Robert
Project Start
2002-07-31
Project End
Budget Start
2003-07-01
Budget End
2004-06-30
Support Year
2
Fiscal Year
2003
Total Cost
$26,644
Indirect Cost
Name
University of Florida
Department
Genetics
Type
Schools of Medicine
DUNS #
969663814
City
Gainesville
State
FL
Country
United States
Zip Code
32611
Li, Hua; Zhang, Xuelian; Fishbein, Lauren et al. (2010) Analysis of steroid hormone effects on xenografted human NF1 tumor schwann cells. Cancer Biol Ther 10:758-64
Fishbein, Lauren; Zhang, Xuelian; Fisher, Lori B et al. (2007) In vitro studies of steroid hormones in neurofibromatosis 1 tumors and Schwann cells. Mol Carcinog 46:512-23