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BSC 589 Independent Studies (3 Credit Hours) – Fall 2012 (Alaa Qur) G1P3-Cytoskeletal Interaction and Cancer Instructor: Dr. Venugopalan Cheriyath, STC 352, STC 353 and STC 332 Purpose: To develop an understanding of the role of interaction of G1P3 and cytoskeletal elements in breast cancer development and progression. Objectives: 1. Conduct literature review on the role of cytoskeletal element actin in cancer development, progression and apoptosis. 2. Grow and maintain MCF-7Vector and MCF-7G1P3 cells in culture. 3. Investigate the effect of G1P3 on actin organization. 4. Investigate the interaction of wild type and mutant G1P3 with actin. 5. Make a research proposal and hopefully present findings at Pathway Symposium and at subsequent scientific meetings Grading Scheme Attendance and Participation 45 Points Cell culture 15 points Immunoblot analysis & Immunoprecipitation 15 points Statistical Analysis 5 points Presentation 10 points Report 10 points Requirements: Student will be working under my direct supervision. Student is required to attend all lab meetings and work at least 20 hours of laboratory work per week. Depending on the experiments they may require to come to the everyday of the week including week ends. Important References 1. Cheriyath, V., Kuhns, M.A., Jacobs, B.S., Evangelista, P., Downs-Kelly, E., Tubbs, R., Huang, T.M., and Borden, E.C. 2011. G1P3 Overexpression Inhibits Mammary Epithelial 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. Cell Apoptosis to Induce Hyperplasia and Negatively Impacts Clinical Outcome in Breast Cancer Oncogene:In Press. Bharadwaj, S., Thanawala, R., Bon, G., Falcioni, R., and Prasad, G.L. 2005. Resensitization of breast cancer cells to anoikis by tropomyosin-1: role of Rho kinasedependent cytoskeleton and adhesion. Oncogene 24:8291-8303. American Cancer Society. 2011. Cancer Facts & Figures 2010. Atlanta: American Cancer Society. 9 - 11. Marani, M., Hancock, D., Lopes, R., Tenev, T., Downward, J., and Lemoine, N.R. 2004. Role of Bim in the survival pathway induced by Raf in epithelial cells. Oncogene 23:24312441. McConkey, D.J., and Bondar, V. 6 Regulation and Function of Detachment-Induced Cell Death (Anoikis) in Cancer Progression and Metastasis. Reginato, M.J., Mills, K.R., Paulus, J.K., Lynch, D.K., Sgroi, D.C., Debnath, J., Muthuswamy, S.K., and Brugge, J.S. 2003. Integrins and EGFR coordinately regulate the pro-apoptotic protein Bim to prevent anoikis. Nat Cell Biol 5:733-740. Aplin, A.E., Stewart, S.A., Assoian, R.K., and Juliano, R.L. 2001. Integrin-mediated adhesion regulates ERK nuclear translocation and phosphorylation of Elk-1. J Cell Biol 153:273-282. Frisch, S.M., and Screaton, R.A. 2001. Anoikis mechanisms. Curr Opin Cell Biol 13:555562. Debnath, J., Muthuswamy, S.K., and Brugge, J.S. 2003. Morphogenesis and oncogenesis of MCF-10A mammary epithelial acini grown in three-dimensional basement membrane cultures. Methods 30:256-268. Swan, E.A., Jasser, S.A., Holsinger, F.C., Doan, D., Bucana, C., and Myers, J.N. 2003. Acquisition of anoikis resistance is a critical step in the progression of oral tongue cancer. Oral Oncol 39:648-655. Lin, J.J., Warren, K.S., Wamboldt, D.D., Wang, T., and Lin, J.L. 1997. Tropomyosin isoforms in nonmuscle cells. Int Rev Cytol 170:1-38. Pawlak, G., McGarvey, T.W., Nguyen, T.B., Tomaszewski, J.E., Puthiyaveettil, R., Malkowicz, S.B., and Helfman, D.M. 2004. Alterations in tropomyosin isoform expression in human transitional cell carcinoma of the urinary bladder. Int J Cancer 110:368-373. Dunn, G.P., Koebel, C.M., and Schreiber, R.D. 2006. Interferons, immunity and cancer immunoediting. Nat Rev Immunol 6:836-848. Einav, U., Tabach, Y., Getz, G., Yitzhaky, A., Ozbek, U., Amariglio, N., Izraeli, S., Rechavi, G., and Domany, E. 2005. Gene expression analysis reveals a strong signature of an interferon-induced pathway in childhood lymphoblastic leukemia as well as in breast and ovarian cancer. Oncogene 24:6367-6375. Bektas, N., Noetzel, E., Veeck, J., Press, M.F., Kristiansen, G., Naami, A., Hartmann, A., Dimmler, A., Beckmann, M.W., Knuchel, R., et al. 2008. The ubiquitin-like molecule interferon-stimulated gene 15 (ISG15) is a potential prognostic marker in human breast cancer. Breast Cancer Res. 10:R58. 16. 17. 18. 19. 20. 21. 22. Calogero, R.A., Cordero, F., Forni, G., and Cavallo, F. 2007. Inflammation and breast cancer. Inflammatory component of mammary carcinogenesis in ErbB2 transgenic mice. Breast Cancer Res. 9:211. de Visser, K.E., Eichten, A., and Coussens, L.M. 2006. Paradoxical roles of the immune system during cancer development. Nat Rev Cancer 6:24-37. DeNardo, D.G., and Coussens, L.M. 2007. Inflammation and breast cancer. Balancing immune response: crosstalk between adaptive and innate immune cells during breast cancer progression. Breast Cancer Res. 9:212. Luszcek, R., Cheriyath, V., Mekhail, T., and Borden, E. 2010. Combinations of DNA Methyltransferase and Histone Deacetylase Inhibitors Induce DNA Damage in Small Cell Lung Cancer Cells: Correlation of Resistance to Interferon Stimulated Gene Expression Molecular Cancer Therapeutics In Press. Weichselbaum, R.R., Ishwaran, H., Yoon, T., Nuyten, D.S., Baker, S.W., Khodarev, N., Su, A.W., Shaikh, A.Y., Roach, P., Kreike, B., et al. 2008. An interferon-related gene signature for DNA damage resistance is a predictive marker for chemotherapy and radiation for breast cancer. Proc Natl Acad Sci U S A 105:18490-18495. Mailleux, A.A., Overholtzer, M., and Brugge, J.S. 2008. Lumen formation during mammary epithelial morphogenesis: insights from in vitro and in vivo models. Cell Cycle 7:57-62. Weigelt, B., and Bissell, M.J. 2008. Unraveling the microenvironmental influences on the normal mammary gland and breast cancer. Semin Cancer Biol 18:311-321.