Our aim is to determine if estrogen and/or progesterone receptors are present in schwannomas, meingiomas, and neurofibromas as well as in the normal tissues from which these tumors arise. We also will develop a tissue culture system for these tumors in order to test the effects of hormonal manipulation on tumor cell growth in vitro. Schwannomas will be chemically induced in rats in order to study alterations in the sex steroid receptors which may occur with tumorigenesis and to study the in vivo effects of hormonal manipulation. To accomplish these aims we will measure specific estradiol and progesterone binding in frozen specimens of these human tumors. The estrogen binding data will be correlated with a recently developed immunofluorescent technique using purified rabbit anti-estrogen-receptor antibody to detect estrogen receptors. Additionally, meningiomas will be grown in tissue culture. Schwann cells will be purified from schwannoma and neurofibroma specimens using techniques involving co-culture of the tumor with previously-prepared mouse dorsal root ganglion cultures. Both the steroid binding and the immunofluorescent techniques will then be used to detect estrogen and progesterone receptors in the cultured cells. The effects of estradiol, progesterone and Tomoxifen, will be studied on the growth of these cells in vitro. Specimens of normal spinal cord, dorsal root ganglia, nerves, and arachnoidal villi will be studied in rats and in humans (autopsy or surgical specimens) for the presence of estrogen and progesterone receptor. Using nitrosoureas, schwann cell tumors will be induced in rats and tested in a similar fashion in order to detect alterations in estrogen receptors occurring with tumorigenesis. The rats will be subjected to hormonal manipulations to see if tumor growth can be inhibited. The significance of this proposal is underscored by the fact that neurofibromatosis is a common single gene autosomal dominant disorder (1/3,000 births) associated with numerous nervous system tumors (schwannomas, meningiomas, neurofibromas, neurofibrosacromas). To date, there is no treatment for this disorder or for many of its associated tumors. These studies will provide a basis for understanding the pathogenesis and possible hormonal modulation of this disorder and associated tumors and provide the ground work for future hormonal therapy.
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