EVALUATION OF THE EFFECTS OF SMURF1 AND SMURF2 ON TUMOR PROGRESSION

Abstract

The goals of this project are to determine the effects of Smurf1 and Smurf2 E3 ubiquitin ligases on tumor progression, and to access whether a therapeutic treatment of siRNA can reverse these effects. Cancer is a leading cause of death world wide, and specific causes of some forms of this disease are still not well understood. It is thus important to determine specific causes of cancer, and develop new therapies to treat the disease. Essentially, cancer occurs when cells undergo changes that allow them to grow uncontrollably. Smurf1 and Smurf2 have become potential targets of cancer research and therapy for two main reasons. Functionally, they control the levels of some proteins involved in cell growth and development, and clinically they have been found in large amounts in some tumors. In order to accomplish these goals, we will first produce and maintain a colony of mice deficient in Smurf1 and Smurf2. We will then use the DMBA-TPA skin painting technique to determine the effects of these deficiencies on tumor development. We will then analyze the Smad mRNA and protein levels in those tumors. Finally, we will inject athymic nu/nu mice with cell lines over expressing Smurf1 and Smuf2 to determine how an increased presence of Smurf1 and Smurf2 effects tumor grow and/or metastatic potential. These mice will then be given IV injections of Smurf specific SiRNA to see if these effects can be reversed. If these effects can be reversed, SiRNA has the potential to be a highly specific relatively nonhazardous treatment that can be eventually applied to various forms of cancer.