It has been a while since I have updated due to various time commitments of being a third year student from various core modules to the third year dissertation project.
Currently, there are only a few weeks left till the dissertation deadline but I am looking forward to producing my first, hopefully of many, publications using research I have carried out. The dissertation project I am focused on involves neurotensin receptors 1 (NTS1) being over expressed in breast cancer cells. A paper by Vandebulcke et al. (2000) has shown the uptake of neurotensin-GFP fusion into COS-7 breast cancer cells which allows the way for possible targeted drug delivery applications. My project is focusing on the cloning of neurotensin-double GFP fusions using PCR techniques to test the size of the endocytosis uptake by the NTS1 GPCR receptors expressed on COS-7 cells. My supervisor for this project is Dr. Alan Goddard.
Neurotensin receptors are expressed naturally on other tissues mainly in the central nervous system (CNS) shown by Uhl et al. (1977) in rat central nervous system. Targeting and administration of these neurotensin-drug fusions should not enter the CNS due to various efflux receptors, most commonly noted in the blood brain barrier, so theoretically neurotensin offers a unique target for drug delivery. An interesting fusion could be the use of interferon (IFN) alpha with the ability to act as an anti-viral agents which inhibits replication and has shown promise in current cancer treatment (Ferrantini et al., 2007; Zaidi and Merlino, 2011). Due to IFN-alpha protein structure, fusions with neurotensin may be a possible payload to delivery to COS-7 cells.
I am presenting my work via poster at the ‘University of Lincoln Undergraduate Life Sciences Conference 2014’, dates: TBA expected early June. I will post an update when more information becomes available.
Ferrantini, M., Capone, I., and Belardelli, F. (2007) Interferon-alpha and cancer: mechanisms of action and new perspectives of clinical use. Biochimie, 89(6-7), pp. 884-893.
Uhl, G.R.; Kuhar, M.J.; Snyder, S.H. (1977) Neurotensin: immunohistochemical localization in rat central nervous system. Proceedings of the National Academy of Sciences of the United States of America, 74(9), pp. 4059-4063.
Vandenbulcke, F., Nouel, D., Vincent, J.P., Mazella, J., and Beaudet, A. (2000) Ligand-induced internalization of neurotensin in transfected COS-7 cells: differential intracellular trafficking of ligand and receptor. Journal of Cell Science, 113 ( Pt 17)(Pt 17), pp. 2963-2975.
Zaidi, M.R. and Merlino, G. (2011) The two faces of interferon-gamma in cancer. Clinical Cancer Research : An Official Journal of the American Association for Cancer Research, 17(19), pp. 6118-6124.