Molecular Mechanisms of Tumorigenesis in von Hippel-Lindau Disease (FWOTM893)

Cell cycle and proliferation play an important role in the development of human neoplasia and are under control of tumor suppressor genes. Inactivation of both alleles of a tumor suppressor gene is thought to induce tumorigenesis. Patients with hereditary tumor syndromes, like e.g. von Hippel-Lindau (VHL) disease, carry a germline mutation of one allele of a tumor suppressor gene. A somatic mutation of the other allele in any cell of the body is thought to induce tumorigenesis. However, recent studies have shown that biallelic inactivation of the VHL tumor suppressor gene is not sufficient to induce tumorigenesis. The lack of understanding the function of the VHL tumor suppressor gene has precluded the development of pharmacological therapies for the respective tumors.
The aim of the suggested research is to characterize the effects and
consequences of VHL inactivation and to clarify further steps of VHL tumorigenesis on a proteomic level. This will be achieved by proteomic comparison of the cells of origin of VHL tumors, which have recently been identified by the applicant, with
VHL tumors in different stages. Proteins that are identified as possible candidates of promotion of tumorigenesis will be blocked in tumor cell cultures, which is expected to lay the foundation for development of pharmacological therapies for VHL associated tumors.

Keywords:tumoren, Hippel-Lindau

Disciplines:Cancer therapy

Project type:Service project