Funded Grants

Molecular Mechanisms of PKC Functions in the Growth and Apoptosis of Glioma Cells

Gliomas constitute the majority of primary brain tumors. Despite advances in surgical techniques, radiotherapy and chemotherapy the prognosis of patients with gliomas is poor. Thus, further understanding of the molecular processes underlying the tumorigenesis of gliomas is essential for the development of effective treatments.

The development of tumors is associated with impaired control of cell proliferation. Protein kinase C, a family of serine-threonine kinases is involved in carcinogenesis. The expression of specific PKC isoforms is increased in different tumors and overexpression of PKC interferes with cell proliferation, differentiation and apoptosis. PKC is also involved in the tumorigenesis of malignant gliomas, but the identity of the isoforms and the mechanisms involved in their effects are not known. In this study we will explore the mechanisms involved in the effects of specific PKC isoforms on cell growth and differentiation and the interaction of PKCCC with the EGF receptor. These studies will provide important information regarding the cross talk between PKC and tyrosine kinases and how dysregulation of specific isoforms leads to impaired cellular function associated with tumor promotion.

Most malignant gliomas are resistant to cell death induced by drugs and radiation. Thus, delineating the role of PKC in the regulation of glioma cell death has important implications for the use of radiotherapy and chemotherapy in these tumors. In summary, the results of these studies may contribute to the understanding of the roles of PKC in the tumorigenesis of gliomas and to the development of novel therapeutic approaches for the treatment of these tumors.