Yan Tang Department of Pharmacology Tulane University 1430 Tulane Avenue New Orleans, Louisiana 70112 yantangzhao@yahoo.com I am interested in understanding MEK5 signaling pathways which may play a critical role in anti-apoptosis, development of resistance to chemotherapeutic drugs, and change to a hormone independent phenotype in breast cell carcinoma. 1. MEK5 stably expressed in an MCF-7 breast cell line (CA-MEK5) established in this lab, showed a more aggressive growth pattern and more resistant to TNFa-induced apoptosis than parental MCF-7 cells. The ability of cancer cells to resist the cytotoxicity of anti-cancer drugs may be due to the presence or activation of cellular survival signals. Thus tumor cells that possess or acquire these changes would prevent an apoptotic response, promote clonogenic survival/proliferation, and ultimately progress to a more malignant and drug-resistant phenotype. According to our gene expression profile (AFFymetrix) , the study will be focused on how MEK5 regulates the family of anti-apoptotic protein expression. 2. The presence of estrogen receptor (ER) is correlated with a better prognosis both in terms of increased disease-free survival and overall survival and predicts for response to hormonal therapies such as tamoxifen. The impact of MEK5-signaling on the regulation of ER-function and progression to an estrogen- independent phenotype are important in understanding the recurrent and or metastatic breast cancer patients if their primary ER is an alpha subtype. Real-time PCR and immunohistochemistry will be applied to test whether this independence is due to differences in expression of an estrogen receptor, both at the mRNA and protein levels in CA-MEK5. Studies will also focus on whether MEK5 transforms ER subtype phenotypes, or if the downstream signaling of ER is altered. MEK5 expression will also be studied in a group of tamoxifen therapy failed patients to correlate lab findings and clinical cases.     Yan's son with his prize-winning project   NF-kB Plays a Key Role in Hypoxia-Inducible Factor-1-Regulated Erythropoietin Gene Expression Yanira G. Figueroa, Anna K. Chan, Ranira Ibrahim, Yan Tang, Matthew E. Burow, Jawed Alam, Aline B. Scandurro, Barbara S. Beckman download a PDF file of this paper   Yan Tang 's CV download a PDF file of this CV   Yan Tang Selected Publications   Qin, Y.,Tang, Y., A. Schall, and B. Beckman. Dexniguldipine hydrochloride inhibits growth human pancreatic adenocarcinoma cells and expression of Protein Kinase C isoformers alpha and zeta. Int. J. Oncol. 7: 1073-1077. (1995) Burow ME, Weldon CB, Tang Y, McLachlan JA, Beckman BS. Oestrogen-mediated suppression of tumour necrosis factor alpha-induced apoptosis in MCF-7 cells: subversion of Bcl-2 by antioestrogens. J Steroid Biochem Mol Biol 78:409-418, 2001. Figueroa, YG, Chan AK, Ibrahim R, Tang Y, Burow ME, Alam J, Scandurro AB, Beckman BS. NF-B plays a key role in hypoxia-inducible factor-1-regulated erythropoietin gene expression. Expt Hematol 30: 1419-1427, 2002 Kelly, M., Y. Tang, N. Rosensweig, S.Clejan, and B. Beckman. Granulocyte-Macrophage Colony-Stimulating Factor rescued TF-1 leukemia cells from ionizing radiation-induced apoptosis through a pathway mediated by protein kinase C alpha. Blood. 92:416-424. (1998). Burrow, M., C. Weldon, Y. Tang, G. Naver, T. Hammond, S. Clejan, and B. Beckman. Differences in susceptibility to tumor necrosis factor - alpha -induced apoptosis among MCF-7 breast cancer cell variant. Cancer Research. 58:4940-4946. (1998). Mallia, C., V. Aguirre, E. McGary, Y. Tang, A. Scandurro, C. Liu, C. Noguchi, and B. Beckman. Protein kinase C alpha is an effector of hexamethylene bisacetamide-induced differentiation of Friend erythroleukemia cells.  Exp Cell Res. 246:348-354. (1999). Burrow, M., Y. Tang, B. Collins-Burrow, S. Krajewski, J Reed, J. McLachlan, S. Clejan, and B. Beckman. Effects of environmental estrogens on tumor necrosis factor alpha-mediated apoptosis in MCF7 cells. Carcinogenesis. 20:2057-2061. (1999). Burrow, M., C. Weldon, T-C. Chiang, Y. Tang, B. Collins-Burrow, K. Rolfe, S. Li, J. McLachlan, and B. Beckman. Differences in protein kianse C and estrogen receptor alpha, beta expression and signaling correlate with apoptotic sensitivity of MCF-7 breast cancer cell variants. Int. J. Oncol. 16: 1179-1187. (2000). Burrow, M., Weldon, C., Tang Y, J. McLachlan J., and Beckman B. Oestrogen-mediated suppression of tumour necrosis factor alpha-induced apoptosis in MCF-7 cells: subversion of Bcl-2 by anti-oestrogens. J. of Steroid Biochemistry & Molecular Biology. 78:409-418. (2001). Yan Tang, Chris B. Weldon, Steven Elliott, Nancy N. Butler, Jawed Alam, Barbara S. Beckman, Tyler J. Curiel, Matthew E. Burow. Effects of the MEK5 - Erk5 signaling pathway on regulation of cell survival in breast carcinoma cells. American Association for Cancer Research 94th annual meeting, April 5-9 (2003).