Download BSC 589 Independent Studies (3 Credit Hours) – Fall 2012

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
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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.
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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.