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Dennis K Watson, PhD
Professor of Pathology & Laboratory Medicine
College of Medicine
MUSC

Email: watsondk@musc.edu
 
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Dennis K Watson, PhD

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Research Interest:

I have long standing interest and expertise in the areas of cellular and molecular biology, gene discovery, cellular differentiation and molecular oncology. During the initial stages of oncogene discovery, I was among the first to molecularly characterize the viral and cellular myc genes. I was also among the discoverers of the Ets gene family and have been directly responsible for the isolation and characterization of Ets gene products and their role in cellular proliferation, differentiation and etiology of cancer. In addition to continuing to evaluate the role of specific Ets genes in cellular transformation, my laboratory has identified and functionally characterized genes with altered expression during cancer progression. My research program has expertise in using in vitro and in vivo loss of function and gain of function approaches and molecular analyses to examine the functional significance of altered expression and the regulatory networks that such changes control. Recent studies in the laboratory have explored the role of regulatory circuitry in tumor cell interaction with the microenvironment.

Positions:
Associate Director of Education & Training, Hollings Cancer Center, Medical University of South Carolina

Selected Publications:

1.Findlay VJ, Wang C, Watson DK, Camp ER. Epithelial-to-mesenchymal transition and the cancer stem cell phenotype: insights from cancer biology with therapeutic implications for colorectal cancer. Cancer Gene Ther. .21(5):181-7, 2014. PMCID: PMC4041800
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2.Abedin MJ, Nguyen A, Jiang N, Perry CE, Shelton JM, Watson DK, Ferdous A. Fli1 Acts Downstream of Etv2 to Govern Cell Survival and Vascular Homeostasis via Positive Autoregulation. Circ Res. .114(11):1690-9, 2014.
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3.Findlay VJ, Moretz RE, Wang C, Vaena SG, Bandurraga SG, Ashenafi M, Marshall DT, Watson DK, Camp ER. Slug expression inhibits calcitriol-mediated sensitivity to radiation in colorectal cancer. Mol Carcinog. .53 Suppl 1:E130-9, 2013. PMCID: PMC3858479
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4.Suzuki E, Williams S, Sato S, Gilkeson G, Watson DK, Zhang XK. The transcription factor Fli-1 regulates monocyte, macrophage and dendritic cell development in mice. Immunology. .139(3):318-27, 2013. PMCID: PMC3701178
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5.Camp ER, Wang C, Little EC, Watson PM, Pirollo KF, Rait A, Cole DJ, Chang EH, Watson DK. Transferrin receptor targeting nanomedicine delivering wild-type p53 gene sensitizes pancreatic cancer to gemcitabine therapy. Cancer Gene Ther. .20(4):222-8, 2013. PMCID: PMC3746039
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6.Findlay VJ, LaRue AC, Turner DP, Watson PM, Watson DK. Understanding the role of ETS-mediated gene regulation in complex biological processes. Adv Cancer Res. .119:1-61, 2013.
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7.Qin Z, Dai L, Defee M, Findlay VJ, Watson DK, Toole BP, Cameron J, Peruzzi F, Kirkwood K, Parsons C. Kaposi's sarcoma-associated herpesvirus suppression of DUSP1 facilitates cellular pathogenesis following de novo infection. J Virol. .87(1):621-35, 2012. PMCID: PMC3536420
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8.Suzuki E, Karam E, Williams S, Watson DK, Gilkeson G, Zhang XK. Fli-1 transcription factor affects glomerulonephritis development by regulating expression of monocyte chemoattractant protein-1 in endothelial cells in the kidney. Clin Immunol. .145(3):201-8, 2012. PMCID: PMC3501541
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9.Rossa C, Sommer G, Spolidorio LC, Rosenzweig SA, Watson DK, Kirkwood KL. Loss of expression and function of SOCS3 is an early event in HNSCC: altered subcellular localization as a possible mechanism involved in proliferation, migration and invasion. PLoS One. .7(9):e45197, 2012. PMCID: PMC3445460
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10.Little EC, Wang C, Watson PM, Watson DK, Cole DJ, Camp ER. Novel immunocompetent murine models representing advanced local and metastatic pancreatic cancer. J Surg Res. .176(2):359-66, 2011. PMCID: PMC3406409
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11.Moussa O, Ciupek A, Watson DK, Halushka PV. Urinary thromboxane B2 and thromboxane receptors in bladder cancer: opportunity for detection and monitoring. Prostaglandins Other Lipid Mediat. .96(1-4):41-4, 2011. PMCID: PMC3215826
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12.Kornblau SM, Qiu YH, Zhang N, Singh N, Faderl S, Ferrajoli A, York H, Qutub AA, Coombes KR, Watson DK. Abnormal expression of FLI1 protein is an adverse prognostic factor in acute myeloid leukemia. Blood. .118(20):5604-12, 2011. PMCID: PMC3217360
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13.Turner DP, Findlay VJ, Moussa O, Semenchenko VI, Watson PM, LaRue AC, Desouki MM, Fraig M, Watson DK. Mechanisms and functional consequences of PDEF protein expression loss during prostate cancer progression. Prostate. .71(16):1723-35, 2011. PMCID: PMC3128180
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14.Camp ER, Findlay VJ, Vaena SG, Walsh J, Lewin DN, Turner DP, Watson DK. Slug expression enhances tumor formation in a noninvasive rectal cancer model. J Surg Res. .170(1):56-63, 2011. PMCID: PMC3134530
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15.Findlay VJ, Turner DP, Yordy JS, McCarragher B, Shriver MR, Szalai G, Watson PM, Larue AC, Moussa O, Watson DK. Prostate-Derived ETS Factor Regulates Epithelial-to-Mesenchymal Transition through Both SLUG-Dependent and Independent Mechanisms. Genes Cancer. .2(2):120-9, 2011. PMCID: PMC3111250
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16.Moussa O, LaRue AC, Abangan RS, Williams CR, Zhang XK, Masuya M, Gong YZ, Spyropoulos DD, Ogawa M, Gilkeson G, Watson DK. Thrombocytopenia in mice lacking the carboxy-terminal regulatory domain of the Ets transcription factor Fli1. Mol Cell Biol. .30(21):5194-206, 2010. PMCID: PMC2953061
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17.Mathenia J, Reyes-Cortes E, Williams S, Molano I, Ruiz P, Watson DK, Gilkeson GS, Zhang XK. Impact of Fli-1 transcription factor on autoantibody and lupus nephritis in NZM2410 mice. Clin Exp Immunol. .162(2):362-71, 2010. PMCID: PMC2996603
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18.Ogawa M, Larue AC, Watson PM, Watson DK. Hematopoietic stem cell origin of connective tissues. Exp Hematol. .38(7):540-7, 2010.
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19.Ogawa M, Larue AC, Watson PM, Watson DK. Hematopoietic stem cell origin of mesenchymal cells: opportunity for novel therapeutic approaches. Int J Hematol. .91(3):353-9, 2010.
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20.Asano Y, Stawski L, Hant F, Highland K, Silver R, Szalai G, Watson DK, Trojanowska M. Endothelial Fli1 deficiency impairs vascular homeostasis: a role in scleroderma vasculopathy. Am J Pathol. .176(4):1983-98, 2010. PMCID: PMC2843486
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21.Schaefer JS, Sabherwal Y, Shi HY, Sriraman V, Richards J, Minella A, Turner DP, Watson DK, Zhang M. Transcriptional regulation of p21/CIP1 cell cycle inhibitor by PDEF controls cell proliferation and mammary tumor progression. J Biol Chem. .285(15):11258-69, 2010. PMCID: PMC2857004
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22.Moussa O, Turner DP, Feldman RJ, Sementchenko VI, McCarragher BD, Desouki MM, Fraig M, Watson DK. PDEF is a negative regulator of colon cancer cell growth and migration. J Cell Biochem. .108(6):1389-98, 2009. PMCID: PMC3348703
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23.Shirai K, Sera Y, Bulkeley W, Mehrotra M, Moussa O, LaRue AC, Watson DK, Stuart RK, Lazarchick J, Ogawa M. Hematopoietic stem cell origin of human fibroblasts: cell culture studies of female recipients of gender-mismatched stem cell transplantation and patients with chronic myelogenous leukemia. Exp Hematol. .37(12):1464-71, 2009. PMCID: PMC2802494
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24.Kruse EA, Loughran SJ, Baldwin TM, Josefsson EC, Ellis S, Watson DK, Nurden P, Metcalf D, Hilton DJ, Alexander WS, Kile BT. Dual requirement for the ETS transcription factors Fli-1 and Erg in hematopoietic stem cells and the megakaryocyte lineage. Proc Natl Acad Sci U S A. .106(33):13814-9, 2009. PMCID: PMC2728977
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25.Sera Y, LaRue AC, Moussa O, Mehrotra M, Duncan JD, Williams CR, Nishimoto E, Schulte BA, Watson PM, Watson DK, Ogawa M. Hematopoietic stem cell origin of adipocytes. Exp Hematol. .37(9):1108-20, 1120.e1-4, 2009. PMCID: PMC2740899
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26.Elkareh J, Periyasamy SM, Shidyak A, Vetteth S, Schroeder J, Raju V, Hariri IM, El-Okdi N, Gupta S, Fedorova L, Liu J, Fedorova OV, Kahaleh MB, Xie Z, Malhotra D, Watson DK, Bagrov AY, Shapiro JI. Marinobufagenin induces increases in procollagen expression in a process involving protein kinase C and Fli-1: implications for uremic cardiomyopathy. Am J Physiol Renal Physiol. .296(5):F1219-26, 2009. PMCID: PMC2681369
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27.Asano Y, Markiewicz M, Kubo M, Szalai G, Watson DK, Trojanowska M. Transcription factor Fli1 regulates collagen fibrillogenesis in mouse skin. Mol Cell Biol. .29(2):425-34, 2008. PMCID: PMC2612518
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28.Findlay VJ, Turner DP, Moussa O, Watson DK. MicroRNA-mediated inhibition of prostate-derived Ets factor messenger RNA translation affects prostate-derived Ets factor regulatory networks in human breast cancer. Cancer Res. .68(20):8499-506, 2008. PMCID: PMC2680499
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29.Zhang XK, Moussa O, LaRue A, Bradshaw S, Molano I, Spyropoulos DD, Gilkeson GS, Watson DK. The transcription factor Fli-1 modulates marginal zone and follicular B cell development in mice. J Immunol. .181(3):1644-54, 2008. PMCID: PMC2504761
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30.Turner DP, Findlay VJ, Kirven AD, Moussa O, Watson DK. Global gene expression analysis identifies PDEF transcriptional networks regulating cell migration during cancer progression. Mol Biol Cell. .19(9):3745-57, 2008. PMCID: PMC2526691
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31.Moussa O, Ashton AW, Fraig M, Garrett-Mayer E, Ghoneim MA, Halushka PV, Watson DK. Novel role of thromboxane receptors beta isoform in bladder cancer pathogenesis. Cancer Res. .68(11):4097-104, 2008.
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32.Watson PM, Miller SW, Fraig M, Cole DJ, Watson DK, Boylan AM. CaSm (LSm-1) overexpression in lung cancer and mesothelioma is required for transformed phenotypes. Am J Respir Cell Mol Biol. .38(6):671-8, 2008. PMCID: PMC2396246
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33.Turner DP, Watson DK. ETS transcription factors: oncogenes and tumor suppressor genes as therapeutic targets for prostate cancer. Expert Rev Anticancer Ther. .8(1):33-42, 2008.
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34.Turner DP, Findlay VJ, Moussa O, Watson DK. Defining ETS transcription regulatory networks and their contribution to breast cancer progression. J Cell Biochem. .102(3):549-59, 2007.
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35.Moussa O, Riker JM, Klein J, Fraig M, Halushka PV, Watson DK. Inhibition of thromboxane synthase activity modulates bladder cancer cell responses to chemotherapeutic agents. Oncogene. .27(1):55-62, 2007.
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36.Markiewicz M, Asano Y, Znoyko S, Gong Y, Watson DK, Trojanowska M. Distinct effects of gonadectomy in male and female mice on collagen fibrillogenesis in the skin. J Dermatol Sci. .47(3):217-26, 2007. PMCID: PMC2717737
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37.Higuchi T, Bartel FO, Masuya M, Deguchi T, Henderson KW, Li R, Muise-Helmericks RC, Kern MJ, Watson DK, Spyropoulos DD. Thymomegaly, microsplenia, and defective homeostatic proliferation of peripheral lymphocytes in p51-Ets1 isoform-specific null mice. Mol Cell Biol. .27(9):3353-66, 2007. PMCID: PMC1899970
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38.Turner DP, Moussa O, Sauane M, Fisher PB, Watson DK. Prostate-derived ETS factor is a mediator of metastatic potential through the inhibition of migration and invasion in breast cancer. Cancer Res. .67(4):1618-25, 2007.
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39.Szalai G, LaRue AC, Watson DK. Molecular mechanisms of megakaryopoiesis. Cell Mol Life Sci. .63(21):2460-76, 2006.
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40.Pang L, Xue HH, Szalai G, Wang X, Wang Y, Watson DK, Leonard WJ, Blobel GA, Poncz M. Maturation stage-specific regulation of megakaryopoiesis by pointed-domain Ets proteins. Blood. .108(7):2198-206, 2006. PMCID: PMC1895561
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41.Moussa O, Abol-Enein H, Bissada NK, Keane T, Ghoneim MA, Watson DK. Evaluation of survivin reverse transcriptase-polymerase chain reaction for noninvasive detection of bladder cancer. J Urol. .175(6):2312-6, 2006.
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42.Forough R, Weylie B, Collins C, Parker JL, Zhu J, Barhoumi R, Watson DK. Transcription factor Ets-1 regulates fibroblast growth factor-1-mediated angiogenesis in vivo: role of Ets-1 in the regulation of the PI3K/AKT/MMP-1 pathway. J Vasc Res. .43(4):327-37, 2006.
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43.Moussa O, Yordy JS, Abol-Enein H, Sinha D, Bissada NK, Halushka PV, Ghoneim MA, Watson DK. Prognostic and functional significance of thromboxane synthase gene overexpression in invasive bladder cancer. Cancer Res. .65(24):11581-7, 2005.
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44.Bansal R, Watson DK. Surgical delay in acute admissions on warfarin: are we doing enough? Int J Clin Pract. .59(11):1283-8, 2005.
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45.Yan Y, Rubinchik S, Wood AL, Gillanders WE, Dong JY, Watson DK, Cole DJ. Bystander effect contributes to the antitumor efficacy of CaSm antisense gene therapy in a preclinical model of advanced pancreatic cancer. Mol Ther. .13(2):357-65, 2005.
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46.Seth A, Watson DK. ETS transcription factors and their emerging roles in human cancer. Eur J Cancer. .41(16):2462-78, 2005.
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47.Pei H, Li C, Adereth Y, Hsu T, Watson DK, Li R. Caspase-1 is a direct target gene of ETS1 and plays a role in ETS1-induced apoptosis. Cancer Res. .65(16):7205-13, 2005. PMCID: PMC2265436
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48.Fraser MM, Watson PM, Fraig MM, Kelley JR, Nelson PS, Boylan AM, Cole DJ, Watson DK. CaSm-mediated cellular transformation is associated with altered gene expression and messenger RNA stability. Cancer Res. .65(14):6228-36, 2005.
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49.Yan Y, Rubinchik S, Watson PM, Kelley JR, Fraser MM, Wood AL, Dong JY, Gillanders WE, Boylan AM, Watson DK, Cole DJ. Establishing a murine pancreatic cancer CaSm model: up-regulation of CaSm is required for the transformed phenotype of murine pancreatic adenocarcinoma. Mol Ther. .11(3):363-72, 2005.
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50.Zhang XK, Watson DK. The FLI-1 transcription factor is a short-lived phosphoprotein in T cells. J Biochem. .137(3):297-302, 2005.
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51.Yordy JS, Moussa O, Pei H, Chaussabel D, Li R, Watson DK. SP100 inhibits ETS1 activity in primary endothelial cells. Oncogene. .24(5):916-31, 2005.
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52.Hsouna A, Watson DK, Hsu T. Developmental expression pattern of D-ets4, the Drosophila homologue of human Pdef. Gene Expr Patterns. .5(2):285-9, 2004.
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53.Grund EM, Spyropoulos DD, Watson DK, Muise-Helmericks RC. Interleukins 2 and 15 regulate Ets1 expression via ERK1/2 and MNK1 in human natural killer cells. J Biol Chem. .280(6):4772-8, 2004.
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54.Zhang XK, Gallant S, Molano I, Moussa OM, Ruiz P, Spyropoulos DD, Watson DK, Gilkeson G. Decreased expression of the Ets family transcription factor Fli-1 markedly prolongs survival and significantly reduces renal disease in MRL/lpr mice. J Immunol. .173(10):6481-9, 2004.
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55.Jackers P, Szalai G, Moussa O, Watson DK. Ets-dependent regulation of target gene expression during megakaryopoiesis. J Biol Chem. .279(50):52183-90, 2004.
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56.Masuya M, Moussa O, Abe T, Deguchi T, Higuchi T, Ebihara Y, Spyropoulos DD, Watson DK, Ogawa M. Dysregulation of granulocyte, erythrocyte, and NK cell lineages in Fli-1 gene-targeted mice. Blood. .105(1):95-102, 2004.
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57.Yordy JS, Li R, Sementchenko VI, Pei H, Muise-Helmericks RC, Watson DK. SP100 expression modulates ETS1 transcriptional activity and inhibits cell invasion. Oncogene. .23(39):6654-65, 2004.
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58.Carbone GM, Napoli S, Valentini A, Cavalli F, Watson DK, Catapano CV. Triplex DNA-mediated downregulation of Ets2 expression results in growth inhibition and apoptosis in human prostate cancer cells. Nucleic Acids Res. .32(14):4358-67, 2004. PMCID: PMC514370
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59.Hsu T, Trojanowska M, Watson DK. Ets proteins in biological control and cancer. J Cell Biochem. .91(5):896-903, 2004. PMCID: PMC2265084
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60.Feldman RJ, Sementchenko VI, Gayed M, Fraig MM, Watson DK. Pdef expression in human breast cancer is correlated with invasive potential and altered gene expression. Cancer Res. .63(15):4626-31, 2003.
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61.Kubo M, Czuwara-Ladykowska J, Moussa O, Markiewicz M, Smith E, Silver RM, Jablonska S, Blaszczyk M, Watson DK, Trojanowska M. Persistent down-regulation of Fli1, a suppressor of collagen transcription, in fibrotic scleroderma skin. Am J Pathol. .163(2):571-81, 2003. PMCID: PMC1868228
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62.Pei H, Yordy JS, Leng Q, Zhao Q, Watson DK, Li R. EAPII interacts with ETS1 and modulates its transcriptional function. Oncogene. .22(18):2699-709, 2003.
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63.Spyropoulos DD, Bartel FO, Higuchi T, Deguchi T, Ogawa M, Watson DK. Marker-assisted study of genetic background and gene-targeted locus modifiers in lymphopoietic phenotypes. Anticancer Res. .23(3A):2015-26, 2003.
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64.Feldman RJ, Sementchenko VI, Watson DK. The epithelial-specific Ets factors occupy a unique position in defining epithelial proliferation, differentiation and carcinogenesis. Anticancer Res. .23(3A):2125-31, 2003.
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65.Chen Y, Wang J, Fraig MM, Henderson K, Bissada NK, Watson DK, Schweinfest CW. Alterations in PMS2, MSH2 and MLH1 expression in human prostate cancer. Int J Oncol. .22(5):1033-43, 2003.
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66.Kelley JR, Fraser MM, Hubbard JM, Watson DK, Cole DJ. CaSm antisense gene therapy: a novel approach for the treatment of pancreatic cancer. Anticancer Res. .23(3A):2007-13, 2003.
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67.Czuwara-Ladykowska J, Sementchenko VI, Watson DK, Trojanowska M. Ets1 is an effector of the transforming growth factor beta (TGF-beta ) signaling pathway and an antagonist of the profibrotic effects of TGF-beta. J Biol Chem. .277(23):20399-408, 2002.
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68.Kelley JR, Fraser MM, Schweinfest CW, Vournakis JN, Watson DK, Cole DJ. CaSm/gemcitabine chemo-gene therapy leads to prolonged survival in a murine model of pancreatic cancer. Surgery. .130(2):280-8, 2001.
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69.Kawada H, Ito T, Pharr PN, Spyropoulos DD, Watson DK, Ogawa M. Defective megakaryopoiesis and abnormal erythroid development in Fli-1 gene-targeted mice. Int J Hematol. .73(4):463-8, 2001.
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70.Chen Y, Wang J, Fraig MM, Metcalf J, Turner WR, Bissada NK, Watson DK, Schweinfest CW. Defects of DNA mismatch repair in human prostate cancer. Cancer Res. .61(10):4112-21, 2001.
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71.Czuwara-Ladykowska J, Shirasaki F, Jackers P, Watson DK, Trojanowska M. Fli-1 inhibits collagen type I production in dermal fibroblasts via an Sp1-dependent pathway. J Biol Chem. .276(24):20839-48, 2001.
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72.Sementchenko VI, Watson DK. Ets target genes: past, present and future. Oncogene. .19(55):6533-48, 2000.
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73.Li R, Pei H, Watson DK. Regulation of Ets function by protein - protein interactions. Oncogene. .19(55):6514-23, 2000.
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74.Spyropoulos DD, Pharr PN, Lavenburg KR, Jackers P, Papas TS, Ogawa M, Watson DK. Hemorrhage, impaired hematopoiesis, and lethality in mouse embryos carrying a targeted disruption of the Fli1 transcription factor. Mol Cell Biol. .20(15):5643-52, 2000. PMCID: PMC86032
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75.Kelley JR, Brown JM, Frasier MM, Baron PL, Schweinfest CW, Vournakis JN, Watson DK, Cole DJ. The cancer-associated Sm-like oncogene: a novel target for the gene therapy of pancreatic cancer. Surgery. .128(2):353-60, 2000.
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76.Li R, Pei H, Watson DK, Papas TS. EAP1/Daxx interacts with ETS1 and represses transcriptional activation of ETS1 target genes. Oncogene. .19(6):745-53, 2000.
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77.Shirasaki F, Makhluf HA, LeRoy C, Watson DK, Trojanowska M. Ets transcription factors cooperate with Sp1 to activate the human tenascin-C promoter. Oncogene. .18(54):7755-64, 1999.
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