The molecular mechanisms underlying the development of human brain neoplasms remain poorly understood, so that, advances in surgery, radiation and chemotherapy have not successfully impacted on their lethality. There is good evidence that the more malignant varieties of such tumors express multiple chromosomal abnormalities. In some tumors, genetic aberrations have been associated with alterations in growth factors or their receptors. Consistent with this finding, we have recently demonstrated that human glioma cells express high levels of basic fibroblast growth factor (bFGF), a potent mitogen and angiogenic protein. In contrast to other growth factors previously identified in human gliomas, bFGF expression in gliomas is elevated relative to its expression in other human tumor types. this proposal is aimed at testing the hypothesis that the expression of bFGF correlates with a transformed phenotype in malignant human gliomas. We will determine: 1) if bFGF expression is modified in human glioma cells relative to normal glia and other types of brain tumors, 2) if bFGF expression is directly related to the degree of malignancy in human glioma cells, and 3) if alterations in bFGF expression can effect the phenotype of normal and transformed human glial cells. bFGF expression will be studied at the RNA and protein level using polymerase chain reaction and Western blots respectively. A correlation of bFGF expression with the degree of phenotypic malignancy in gliomas could provide a prognostic marker for this tumor. Furthermore, the expression of bFGF and its receptor in glioma cells may provide a potential avenue for interrupting the lethal cycle of glioma growth and invasion.
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