Meningiomas are one of the most common primary tumors in adults and usually considered a benign, surgically curable tumor. But despite surgery and radiation, their recurrence rate remains as high as 20%. Clinical and experimental studies suggest that meningiomas are hormonally responsive tumors. Yet each year, millions of women use exogenous steroids for the purpose of birth control or the treatment of osteoporosis and menopause, although the effects of these hormones on the development or exacerbation of CNS tumors has not been adequately studied. We have previously demonstrated the presence of hormone receptors in CNS tumors. We further investigated the role that certain growth factors, specifically the insulin-like growth factors (IGFs) play as autocrine factors in CNS tumors. Since sex steroids regulate the expression of IGFs and IGF binding proteins (BPs) in other hormonally responsive tumors, such as breast cancer, we now propose studies which will examine the hormonal regulation of IGF and IGFBP expression in CNS tumors. IGF/IGFBP gene expression will be investigated by northern blotting of mRNA extracted from fresh frozen CNS tumors and correlated with tumor growth and gene expression in an in vivo nude mouse model, in the presence and absence of steroid hormones (estrogen and progesterone) and antihormonal agents (tamoxifen and RU486). Direct effects of sex steroids on IGF/IGFBP production will be examined in vitro by radioimmunoassay of tumor cell conditioned media obtained from CNS tumor cells grown in the presence and absence of steroid hormones and antihormonal agents. These studies will provide an understanding of the hormonal regulation of growth factors in CNS tumor growth, especially as they affect women, and will be the basis for future investigations regarding the development of better """"""""targeted"""""""" therapies for these tumors and for tumor prevention strategies.
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