Date of Award
Master of Science (MS)
College of Science and Mathematics
Thesis Sponsor/Dissertation Chair/Project Chair
Carlos A. Molina
Sandra D. Adams
Quinn C. Vega
There is compelling evidence supporting Inducible cAMP Early Repressor (ICER) as a potent anti-proliferative and potential tumor suppressor protein. ICER is a dominant negative transcription factor that is inducible upon cAMP level increase and represses genes important for cell-cycle regulation, proliferation and differentiation. This thesis discusses the evidence in support of ICER as a tumor suppressor gene product and elucidates mechanisms by which cancer cells that express ICER can nullify its antiproliferative properties. Interestingly, when ICER is put back in the nucleus of particular cancer cells where it works to repress cAMP genes, these cells have impaired tumorigenicity.
This thesis puts forth a model to utilize ICER’s tumor suppressing properties surrounding the introduction or maintenance of nuclear ICER which is cell-type and ICER expression-dependent. In cells expressing detectable ICER levels, the mode of action is to prevent the cell from neutralizing or degrading ICER allowing ICER to remain in the nucleus to repress important mitotic genes. Low ICER-expressing cells will have ICER introduced into the cell using a novel fusion protein constructed to both allow ICER to enter the cell and be transported to the nucleus and be targeted for a specific cancer cell type; a cancer cell that expresses non-self proteins, viral proteins. The chimera was generated to target a cervical carcinoma cell line that is positive for HPV type 18, the HeLa cell.
Crow, Marni, "Evidence That Inducible Cyclic AMP Early Repressor Is a Potent Tumor Suppressor Protein That May Hold Therapeutic Promise for Targeted Therapy of Various Malignancies" (2012). Theses, Dissertations and Culminating Projects. 803.