Vanderbilt University School of
698 Preston Research Building
698 Preston Research Building 37232-6838
Colon Cancer Prevention, COX-2, Novel molecular targets, Angiogenesis, PGE2, Metastatic spread of disease,Apoptosis,Cancer,Genomics,Molecular medicine,Phosphorylation,Receptor,Signal transduction,Transformation
Our laboratory is studying the role of the enzyme cyclooxygenase in the regulation of intestinal epithelial cell growth and transformation. Cyclooxygenase (COX), a key enzyme in the prostaglandin biosynthetic pathway, is transcribed from two distinct genes, COX- I and COX-2. COX-2 is also a member of a family of genes called "immediate early" or "early growth response" genes, and many immediate early genes have been found to be proto-oncogenes like c-fos and c-jun. Likewise, COX-2 is thought to play an important role in the development of intestinal neoplasms.
We have demonstrated that COX-2 expression is markedly increased in 85-90% of human colorectal adenocarcinomas as well as in two rodent models of colorectal carcinogenesis. Interestingly, several epidemiological studies have reported a 40-50% reduction in the risk of developing colorectal cancer in persons who take non-steroidal anti-inflammatory drugs (NSAIDs), such as aspirin, which are classic inhibitors of cyclooxygenase. These results suggest that COX-2 contributes to the development of intestinal tumors, and this hypothesis is supported by the demonstration that mice null for COX-2 have an 86% reduction in tumor multiplicity in a background containing a mutation in the tumor suppressor gene, APC.
Using zebrafish we have found an important role of COX-1 in early kidney development and in vasculogenesis. We are exploring this model to understand the role of eicosanoid signaling in organogenesis and are attempting to develop a fish model of intestinal cancer.
We are continuing to investigate the role that COX is playing in the regulation of epithelial cell growth and tumorigenesis. Recent studies indicate that COX-1, as well as COX-2, are playing an important role in tumorigenesis through effects on cell proliferation as well as angiogenesis and our long term goal is to understand the downstream signaling pathways through which these processes are regulated. We have recently discovered several novel targets for cancer prevention and treatment using this approach. One of these includes the PPARdelta nuclear receptor. We have also found that prostaglandin signaling indirectly activates the EGFR pathway and that targeting both pathways may be much more effective. Pre-clinical studies are underway to determine the potential role of these targets for new cancer treatment options.
Familial cancer syndromes, cancer risk and screening
Cha, YI, DuBois, RN. NSAIDs and cancer prevention: targets downstream of COX-2. Annu Rev Med, 58, 239-52, 2007.
Wang, D, DuBois, RN. Inflammatory mediators and nuclear receptor signaling in colorectal cancer. Cell Cycle, 6(6), 682-5, 2007.
Batts, LE, Polk, DB, Dubois, RN, Kulessa, H. Bmp signaling is required for intestinal growth and morphogenesis. Dev Dyn, 235(6), 1563-70, 2006.
Buchanan, FG, DuBois, RN. Connecting COX-2 and Wnt in cancer. Cancer Cell, 9(1), 6-8, 2006.
Buchanan, FG, DuBois, RN. Emerging roles of beta-arrestins. Cell Cycle, 5(18), 2060-3, 2006.
Buchanan, FG, Gorden, DL, Matta, P, Shi, Q, Matrisian, LM, DuBois, RN. Role of beta-arrestin 1 in the metastatic progression of colorectal cancer. Proc Natl Acad Sci U S A, 103(5), 1492-7, 2006. PMCID:1360588
Cha, YI, Kim, SH, Sepich, D, Buchanan, FG, Solnica-Krezel, L, DuBois, RN. Cyclooxygenase-1-derived PGE2 promotes cell motility via the G-protein-coupled
EP4 receptor during vertebrate gastrulation. Genes Dev, 20(1), 77-86, 2006. PMCID:1356102
Cha, YI, Solnica-Krezel, L, DuBois, RN. Fishing for prostanoids: deciphering the developmental functions of cyclooxygenase-derived
prostaglandins. Dev Biol, 289(2), 263-72, 2006.
DuBois, RN. Cancer prevention: strategy for the future. Carcinogenesis, 27(6), 1126-7, 2006.
DuBois, RN. NSAIDs and prostate cancer risk. Cancer J, 12(2), 108-9, 2006.
Holla, VR, Mann, JR, Shi, Q, DuBois, RN. Prostaglandin E2 regulates the nuclear receptor NR4A2 in colorectal cancer. J Biol Chem, 281(5), 2676-82, 2006.
Mann, JR, Backlund, MG, Buchanan, FG, Daikoku, T, Holla, VR, Rosenberg, DW, Dey, SK, DuBois, RN. Repression of prostaglandin dehydrogenase by epidermal growth factor and snail
increases prostaglandin E2 and promotes cancer progression. Cancer Res, 66(13), 6649-56, 2006.
Wang, D, Dubois, RN. Prostaglandins and cancer. Gut, 55(1), 115-22, 2006. PMCID:1856377
Wang, D, Wang, H, Brown, J, Daikoku, T, Ning, W, Shi, Q, Richmond, A, Strieter, R, Dey, SK, DuBois, RN. CXCL1 induced by prostaglandin E2 promotes angiogenesis in colorectal cancer. J Exp Med, 203(4), 941-51, 2006. PMCID:2118273
Wang, D, Wang, H, Guo, Y, Ning, W, Katkuri, S, Wahli, W, Desvergne, B, Dey, SK, DuBois, RN. Crosstalk between peroxisome proliferator-activated receptor delta and VEGF
stimulates cancer progression. Proc Natl Acad Sci U S A, 103(50), 19069-74, 2006. PMCID:1748178
Backlund, MG, Mann, JR, Dubois, RN. Mechanisms for the prevention of gastrointestinal cancer: the role of prostaglandin
E2. Oncology, 69 Suppl 1, 28-32, 2005.
Backlund, MG, Mann, JR, Holla, VR, Buchanan, FG, Tai, HH, Musiek, ES, Milne, GL, Katkuri, S, DuBois, RN. 15-Hydroxyprostaglandin dehydrogenase is down-regulated in colorectal cancer. J Biol Chem, 280(5), 3217-23, 2005. PMCID:1847633
Brown, JR, DuBois, RN. COX-2: a molecular target for colorectal cancer prevention. J Clin Oncol, 23(12), 2840-55, 2005.
Buchanan, FG, McReynolds, M, Couvillon, A, Kam, Y, Holla, VR, Dubois, RN, Exton, JH. Requirement of phospholipase D1 activity in H-RasV12-induced transformation. Proc Natl Acad Sci U S A, 102(5), 1638-42, 2005. PMCID:547811
Cha, YI, Kim, SH, Solnica-Krezel, L, Dubois, RN. Cyclooxygenase-1 signaling is required for vascular tube formation during development. Dev Biol, 282(1), 274-83, 2005.
Daikoku, T, Wang, D, Tranguch, S, Morrow, JD, Orsulic, S, DuBois, RN, Dey, SK. Cyclooxygenase-1 is a potential target for prevention and treatment of ovarian
epithelial cancer. Cancer Res, 65(9), 3735-44, 2005. PMCID:2584020
Dannenberg, AJ, Lippman, SM, Mann, JR, Subbaramaiah, K, DuBois, RN. Cyclooxygenase-2 and epidermal growth factor receptor: pharmacologic targets
for chemoprevention. J Clin Oncol, 23(2), 254-66, 2005.
Holla, VR, Wang, D, Brown, JR, Mann, JR, Katkuri, S, DuBois, RN. Prostaglandin E2 regulates the complement inhibitor CD55/decay-accelerating
factor in colorectal cancer. J Biol Chem, 280(1), 476-83, 2005.
Komatsu, K, Buchanan, FG, Katkuri, S, Morrow, JD, Inoue, H, Otaka, M, Watanabe, S, DuBois, RN. Oncogenic potential of MEK1 in rat intestinal epithelial cells is mediated
via cyclooxygenase-2. Gastroenterology, 129(2), 577-90, 2005.
Mann, JR, Backlund, MG, DuBois, RN. Mechanisms of disease: Inflammatory mediators and cancer prevention. Nat Clin Pract Oncol, 2(4), 202-10, 2005.
Musiek, ES, Gao, L, Milne, GL, Han, W, Everhart, MB, Wang, D, Backlund, MG, DuBois, RN, Zanoni, G, Vidari, G, Blackwell, TS, Morrow, JD. Cyclopentenone isoprostanes inhibit the inflammatory response in macrophages. J Biol Chem, 280(42), 35562-70, 2005.
Peek, RM, Mohla, S, DuBois, RN. Inflammation in the genesis and perpetuation of cancer: summary and recommendations
from a national cancer institute-sponsored meeting. Cancer Res, 65(19), 8583-6, 2005.
Wang D., Wang H., Brown J., Daikoku T., Dey SK, DuBois RN . GRO is a novel target for PGE2 signaling in colorectal cancer. Cancer Cell, , , 2005.
Wang, D, Buchanan, FG, Wang, H, Dey, SK, DuBois, RN. Prostaglandin E2 enhances intestinal adenoma growth via activation of the Ras-mitogen-activated
protein kinase cascade. Cancer Res, 65(5), 1822-9, 2005.
Wang, D, Mann, JR, DuBois, RN. The role of prostaglandins and other eicosanoids in the gastrointestinal tract. Gastroenterology, 128(5), 1445-61, 2005.
Brown, JR, DuBois, RN. Cyclooxygenase-2 in lung carcinogenesis and chemoprevention: Roger S. Mitchell
lecture. Chest, 125(5 Suppl), 134S-40S, 2004.
Brown, JR, DuBois, RN. Cyclooxygenase as a target in lung cancer. Clin Cancer Res, 10(12 Pt 2), 4266s-4269s, 2004.
Buchanan, FG, Chang, W, Sheng, H, Shao, J, Morrow, JD, DuBois, RN. Up-regulation of the enzymes involved in prostacyclin synthesis via Ras induces
vascular endothelial growth factor. Gastroenterology, 127(5), 1391-400, 2004.
Gupta, Rajnish A, Wang, Dingzhi, Katkuri, Sharada, Wang, Haibin, Dey, Sudhansu K, DuBois, Raymond N. Activation of nuclear hormone receptor peroxisome proliferator-activated receptor-delta accelerates intestinal adenoma growth. Nat Med, 10(3), 245-7, 2004.
Mann, JR, DuBois, RN. Cyclooxygenase-2 and gastrointestinal cancer. Cancer J, 10(3), 145-52, 2004.
Wang H., Guo Y., Wang D., Kingsley P., Marnett L., Das S., DuBois R.N., Dey, S.K. . Aberrant cannabinoid signaling impairs oviductal transport of embryos. Nature Medicine, 10, 1074 - 1080, 2004.
Wang, D, Dubois, RN. Cyclooxygenase-2: a potential target in breast cancer. Semin Oncol, 31(1 Suppl 3), 64-73, 2004.
Wang, D, Mann, JR, DuBois, RN. WNT and cyclooxygenase-2 cross-talk accelerates adenoma growth. Cell Cycle, 3(12), 1512-5, 2004.
Wang, D, Wang, H, Shi, Q, Katkuri, S, Walhi, W, Desvergne, B, Das, SK, Dey, SK, DuBois, RN. Prostaglandin E(2) promotes colorectal adenoma growth via transactivation of
the nuclear peroxisome proliferator-activated receptor delta. Cancer Cell, 6(3), 285-95, 2004.
Wang, Dingzhi, DuBois, Raymond N. Cyclooxygenase 2-derived prostaglandin E2 regulates the angiogenic switch. Proc Natl Acad Sci U S A, 101(2), 415-6, 2004. PMCID:327160
Wang, H, Guo, Y, Wang, D, Kingsley, PJ, Marnett, LJ, Das, SK, DuBois, RN, Dey, SK. Aberrant cannabinoid signaling impairs oviductal transport of embryos. Nat Med, 10(10), 1074-80, 2004.
Yoshinaga, M, Buchanan, FG, DuBois, RN. 15-LOX-1 inhibits p21 (Cip/WAF 1) expression by enhancing MEK-ERK 1/2 signaling
in colon carcinoma cells. Prostaglandins Other Lipid Mediat, 73(1-2), 111-22, 2004.
Buchanan, F Gregory, Wang, Dingzhi, Bargiacchi, Francesca, DuBois, Raymond N. Prostaglandin E2 regulates cell migration via the intracellular activation of the epidermal growth factor receptor. J Biol Chem, 278(37), 35451-7, 2003.
Daikoku, T, Matsumoto, H, Gupta, RA, Das, SK, Gassmann, M, DuBois, RN, Dey, SK. Expression of hypoxia-inducible factors in the peri-implantation mouse uterus
is regulated in a cell-specific and ovarian steroid hormone-dependent manner. Evidence for differential
function of HIFs during early pregnancy. J Biol Chem, 278(9), 7683-91, 2003.
DuBois, R, Wallace, MC. The emerging role and potential of COX-2 inhibitors. Clin Adv Hematol Oncol, 1(2), 97-8, 2003.
DuBois, RN. Cyclooxygenase-2 and colorectal cancer. Prog Exp Tumor Res, 37, 124-37, 2003.
Gupta, Rajnish A, Sarraf, Pasha, Brockman, Jeffrey A, Shappell, Scott B, Raftery, Laurel A, Willson, Timothy M, DuBois, Raymond N. Peroxisome proliferator-activated receptor gamma and transforming growth factor-beta pathways inhibit intestinal epithelial cell growth by regulating levels of TSC-22. J Biol Chem, 278(9), 7431-8, 2003.
Gupta, Rajnish A, Sarraf, Pasha, Mueller, Elisabetta, Brockman, Jeffrey A, Prusakiewicz, Jeffery J, Eng, Charis, Willson, Timothy M, DuBois, Raymond N. Peroxisome proliferator-activated receptor gamma-mediated differentiation: a mutation in colon cancer cells reveals divergent and cell type-specific mechanisms. J Biol Chem, 278(25), 22669-77, 2003.
Gupta, Rajnish A, Tejada, Lovella V, Tong, Beverly J, Das, Sanjoy K, Morrow, Jason D, Dey, Sudhansu K, DuBois, Raymond N. Cyclooxygenase-1 is overexpressed and promotes angiogenic growth factor production in ovarian cancer. Cancer Res, 63(5), 906-11, 2003.
Lee SH, Williams MV, DuBois RN, Blair IA. Targeted lipidpmics usin gelectron cepture atmospheric pressure chemical ionization mass spectrometry. Rapid Comm in Mass Spectrometry, 17, 2168-2176, 2003.
Wagenaar-Miller, RA, Hanley, G, Shattuck-Brandt, R, DuBois, RN, Bell, RL, Matrisian, LM, Morgan, DW. Cooperative effects of matrix metalloproteinase and cyclooxygenase-2 inhibition
on intestinal adenoma reduction. Br J Cancer, 88(9), 1445-52, 2003. PMCID:2741031
DuBois, RN. Modern academic medicine. Am J Med Sci, 324(2), 55-6, 2002.
Gupta, RA, DuBois, RN, Wallace, MC. New avenues for the prevention of colorectal cancer: targeting cyclo-oxygenase-2
activity. Best Pract Res Clin Gastroenterol, 16(6), 945-56, 2002.
Gupta, RA, Dubois, RN. Controversy: PPARgamma as a target for treatment of colorectal cancer. Am J Physiol Gastrointest Liver Physiol, 283(2), G266-9, 2002.
Kozak, KR, Gupta, RA, Moody, JS, Ji, C, Boeglin, WE, DuBois, RN, Brash, AR, Marnett, LJ. 15-Lipoxygenase metabolism of 2-arachidonylglycerol. Generation of a peroxisome
proliferator-activated receptor alpha agonist. J Biol Chem, 277(26), 23278-86, 2002.
Marnett, LJ, DuBois, RN. COX-2: a target for colon cancer prevention. Annu Rev Pharmacol Toxicol, 42, 55-80, 2002.
Shao, Jinyi, Sheng, Hongmiao, DuBois, Raymond N. Peroxisome proliferator-activated receptors modulate K-Ras-mediated transformation of intestinal epithelial cells. Cancer Res, 62(11), 3282-8, 2002.
DuBois, RN. New paradigms for cancer prevention. Carcinogenesis, 22(5), 691-2, 2001.
Dubois, RN. Nonsteroidal antiinflammatory drugs, cyclooxygenase-2, and colorectal cancer
prevention. Curr Opin Gastroenterol, 17(1), 65-71, 2001.
Gupta, R A, Brockman, J A, Sarraf, P, Willson, T M, DuBois, R N. Target genes of peroxisome proliferator-activated receptor gamma in colorectal cancer cells. J Biol Chem, 276(32), 29681-7, 2001.
Gupta, R A, Dubois, R N. Colorectal cancer prevention and treatment by inhibition of cyclooxygenase-2. Nat Rev Cancer, 1(1), 11-21, 2001.
Gupta, RA, Polk, DB, Krishna, U, Israel, DA, Yan, F, DuBois, RN, Peek, RM. Activation of peroxisome proliferator-activated receptor gamma suppresses nuclear
factor kappa B-mediated apoptosis induced by Helicobacter pylori in gastric epithelial cells. J Biol Chem, 276(33), 31059-66, 2001.
Kandil, HM, Tanner, G, Smalley, W, Halter, S, Radhika, A, Dubois, RN. Cyclooxygenase-2 expression in Barrett''s esophagus. Dig Dis Sci, 46(4), 785-9, 2001.
Krause, WF, DuBois, RN. The molecular basis for prevention of colorectal cancer. Clin Colorectal Cancer, 1(1), 47-54, 2001.
Mann, M, Sheng, H, Shao, J, Williams, C S, Pisacane, P I, Sliwkowski, M X, DuBois, R N. Targeting cyclooxygenase 2 and HER-2/neu pathways inhibits colorectal carcinoma growth. Gastroenterology, 120(7), 1713-9, 2001.
Pyo, H, Choy, H, Amorino, GP, Kim, JS, Cao, Q, Hercules, SK, DuBois, RN. A selective cyclooxygenase-2 inhibitor, NS-398, enhances the effect of radiation
in vitro and in vivo preferentially on the cells that express cyclooxygenase-2. Clin Cancer Res, 7(10), 2998-3005, 2001.
Shappell, SB, Gupta, RA, Manning, S, Whitehead, R, Boeglin, WE, Schneider, C, Case, T, Price, J, Jack, GS, Wheeler, TM, Matusik, RJ, Brash, AR, Dubois, RN. 15S-Hydroxyeicosatetraenoic acid activates peroxisome proliferator-activated
receptor gamma and inhibits proliferation in PC3 prostate carcinoma cells. Cancer Res, 61(2), 497-503, 2001.
Sheng RA, Tan J, Krause WF, Gerci MF, Willson TM, Sey SK and DuBois RN. Prostasglandin E2 increases invasiveness of colorectal carcinoma cells. J. Biol. Chem., 276, 18075-18081, 2001.
Sheng, H, Shao, J, DuBois, R N. Akt/PKB activity is required for Ha-Ras-mediated transformation of intestinal epithelial cells. J Biol Chem, 276(17), 14498-504, 2001.
Sheng, H, Shao, J, Dubois, R N. K-Ras-mediated increase in cyclooxygenase 2 mRNA stability involves activation of the protein kinase B1. Cancer Res, 61(6), 2670-5, 2001.
Sheng, H, Shao, J, Washington, MK, DuBois, RN. Prostaglandin E2 increases growth and motility of colorectal carcinoma cells. J Biol Chem, 276(21), 18075-81, 2001.
Stack, E, DuBois, RN. Role of cyclooxygenase inhibitors for the prevention of colorectal cancer. Gastroenterol Clin North Am, 30(4), 1001-10, 2001.
Stack, E, DuBois, RN. Regulation of cyclo-oxygenase-2. Best Pract Res Clin Gastroenterol, 15(5), 787-800, 2001.
Williams, CS, Sheng, H, Brockman, JA, Armandla, R, Shao, J, Washington, MK, Elkahloun, AG, DuBois, RN. A cyclooxygenase-2 inhibitor (SC-58125) blocks growth of established human
colon cancer xenografts. Neoplasia, 3(5), 428-36, 2001. PMCID:1506203
Zhang, Z, DuBois, R N. Detection of differentially expressed genes in human colon carcinoma cells treated with a selective COX-2 inhibitor. Oncogene, 20(33), 4450-6, 2001.
Zhang, Z, Sheng, H, Shao, J, Beauchamp, RD, DuBois, RN. Posttranscriptional regulation of cyclooxygenase-2 in rat intestinal epithelial
cells. Neoplasia, 2(6), 523-30, 2001. PMCID:1508084
Dubois, RN. Review article: cyclooxygenase--a target for colon cancer prevention. Aliment Pharmacol Ther, 14 Suppl 1, 64-7, 2000.
Gupta RA, Tan J, Krause WF, Geraci MF, Willson TM, Dey SK, and DuBois RN. Prostacyclin-mediated activation of PPAR in colorectal cancer. Proc. Natl. Acad. Sci. USA, 97, 13275-13280, 2000.
Gupta, RA, DuBois, RN. Translational studies on Cox-2 inhibitors in the prevention and treatment of
colon cancer. Ann N Y Acad Sci, 910, 196-204; discussion 204-6, 2000.
Gupta, RA, Tan, J, Krause, WF, Geraci, MW, Willson, TM, Dey, SK, DuBois, RN. Prostacyclin-mediated activation of peroxisome proliferator-activated receptor
delta in colorectal cancer. Proc Natl Acad Sci U S A, 97(24), 13275-80, 2000. PMCID:27215
Krause, W, DuBois, RN. Eicosanoids and the large intestine. Prostaglandins Other Lipid Mediat, 61(3-4), 145-61, 2000.
Shao J, Sheng, H, Inoue H, Morrow JD, and DuBois RN. Regulation of Constitutive Cyclooxygenase-2 Expression in Colon Carcinoma Cells. JBC, 275, 33951-33956, 2000.
Shao, J, Sheng, H, DuBois, RN, Beauchamp, RD. Oncogenic Ras-mediated cell growth arrest and apoptosis are associated with
increased ubiquitin-dependent cyclin D1 degradation. J Biol Chem, 275(30), 22916-24, 2000.
Shao, J, Sheng, H, Inoue, H, Morrow, JD, DuBois, RN. Regulation of constitutive cyclooxygenase-2 expression in colon carcinoma cells. J Biol Chem, 275(43), 33951-6, 2000.
Shattuck-Brandt, R L, Varilek, G W, Radhika, A, Yang, F, Washington, M K, DuBois, R N. Cyclooxygenase 2 expression is increased in the stroma of colon carcinomas from IL-10(-/-) mice. Gastroenterology, 118(2), 337-45, 2000.
Sheng, H, Shao, J, Dixon, DA, Williams, CS, Prescott, SM, DuBois, RN, Beauchamp, RD. Transforming growth factor-beta1 enhances Ha-ras-induced expression of cyclooxygenase-2
in intestinal epithelial cells via stabilization of mRNA. J Biol Chem, 275(9), 6628-35, 2000.
Steinbach G, Lynch PM, Phillips RK, Wallace MH, Hawk E, Gordan GB, Wakabayashi N, Saunders B, Shen Y, Fujimura T, Su, L, Levin B, DuBois, Hittelman WH, Zimmerman S, Sherman JW and Kelloff G. The Effect of Celecoxib, a Cox-2 Inhibitor, in Familial Adenomatous Polyposis . N. Engl. J. Med., 342, 1946-1952, 2000.
Williams, C S, Tsujii, M, Reese, J, Dey, S K, DuBois, R N. Host cyclooxygenase-2 modulates carcinoma growth. J Clin Invest, 105(11), 1589-94, 2000. PMCID:300858
Williams, C S, Watson, A J, Sheng, H, Helou, R, Shao, J, DuBois, R N. Celecoxib prevents tumor growth in vivo without toxicity to normal gut: lack of correlation between in vitro and in vivo models. Cancer Res, 60(21), 6045-51, 2000.
Zhang, Z, DuBois, RN. Par-4, a proapoptotic gene, is regulated by NSAIDs in human colon carcinoma
cells. Gastroenterology, 118(6), 1012-7, 2000.
DuBOIS, RN. COX-2 in large bowel cancer: a one-sided story. Gut, 45(5), 636-7, 1999. PMCID:1727709
Shao J, Sheng H, Radhika A, Pereira MA, Lubert R, Hawk E, Grogan L, Lamps L, Kirsch I, Washington MK, Beauchamp RD and DuBois RN. Coordinate Regulation of Cyclooxgenase-2 and TGF-β1 in Hereditary Nonpolyposis Colorectal Cancer and Azoxymethane-Induced Rat Colonic Tumore. Carcinogenesis, 20, 185-191, 1999.
Shao, J, Sheng, H, Aramandla, R, Pereira, MA, Lubet, RA, Hawk, E, Grogan, L, Kirsch, IR, Washington, MK, Beauchamp, RD, DuBois, RN. Coordinate regulation of cyclooxygenase-2 and TGF-beta1 in replication error-positive
colon cancer and azoxymethane-induced rat colonic tumors. Carcinogenesis, 20(2), 185-91, 1999.
Shattuck-Brandt, RL, Dubois, RN. The molecular basis of colorectal carcinogenesis. Curr Opin Gastroenterol, 15(1), 3, 1999.
Shattuck-Brandt, RL, Lamps, LW, Heppner Goss, KJ, DuBois, RN, Matrisian, LM. Differential expression of matrilysin and cyclooxygenase-2 in intestinal and
colorectal neoplasms. Mol Carcinog, 24(3), 177-87, 1999.
Sheng, H, Shao, J, O''Mahony, CA, Lamps, L, Albo, D, Isakson, PC, Berger, DH, DuBois, RN, Beauchamp, RD. Transformation of intestinal epithelial cells by chronic TGF-beta1 treatment
results in downregulation of the type II TGF-beta receptor and induction of cyclooxygenase-2. Oncogene, 18(4), 855-67, 1999.
Williams, C, Shattuck-Brandt, RL, DuBois, RN. The role of COX-2 in intestinal cancer. Ann N Y Acad Sci, 889, 72-83, 1999.
Williams, CS, Goldman, AP, Sheng, H, Morrow, JD, DuBois, RN. Sulindac sulfide, but not sulindac sulfone, inhibits colorectal cancer growth. Neoplasia, 1(2), 170-6, 1999. PMCID:1508136
Williams, CS, Mann, M, DuBois, RN. The role of cyclooxygenases in inflammation, cancer, and development. Oncogene, 18(55), 7908-16, 1999.
Williams, CS, Shattuck-Brandt, RL, DuBois, RN. The role of COX-2 in intestinal cancer. Expert Opin Investig Drugs, 8(1), 1-12, 1999.
Brockman JA, Gupta RA, and Dubois RN . Activation of PPAR Leads to Inhibition of Achorage Independent Growth of Human Colorectal Cancer Cells. Gastroenterology, 115, 1049-1055, 1998.
Brockman, JA, Gupta, RA, Dubois, RN. Activation of PPARgamma leads to inhibition of anchorage-independent growth
of human colorectal cancer cells. Gastroenterology, 115(5), 1049-55, 1998.
DuBois, RN, Gupta, R, Brockman, J, Reddy, BS, Krakow, SL, Lazar, MA. The nuclear eicosanoid receptor, PPARgamma, is aberrantly expressed in colonic
cancers. Carcinogenesis, 19(1), 49-53, 1998.
Dubois, RN, Abramson, SB, Crofford, L, Gupta, RA, Simon, LS, Van De Putte, LB, Lipsky, PE. Cyclooxygenase in biology and disease. FASEB J, 12(12), 1063-73, 1998.
Goldman, AP, Williams, CS, Sheng, H, Lamps, LW, Williams, VP, Pairet, M, Morrow, JD, DuBois, RN. Meloxicam inhibits the growth of colorectal cancer cells. Carcinogenesis, 19(12), 2195-9, 1998.
Sheng, H, Shao, J, Morrow, J D, Beauchamp, R D, DuBois, R N. Modulation of apoptosis and Bcl-2 expression by prostaglandin E2 in human colon cancer cells. Cancer Res, 58(2), 362-6, 1998.
Sheng, H, Shao, J, Williams, CS, Pereira, MA, Taketo, MM, Oshima, M, Reynolds, AB, Washington, MK, DuBois, RN, Beauchamp, RD. Nuclear translocation of beta-catenin in hereditary and carcinogen-induced
intestinal adenomas. Carcinogenesis, 19(4), 543-9, 1998.
Sheng, H, Williams, CS, Shao, J, Liang, P, DuBois, RN, Beauchamp, RD. Induction of cyclooxygenase-2 by activated Ha-ras oncogene in Rat-1 fibroblasts
and the role of mitogen-activated protein kinase pathway. J Biol Chem, 273(34), 22120-7, 1998.
Tsujii, M, Kawano, S, Tsuji, S, Sawaoka, H, Hori, M, DuBois, R N. Cyclooxygenase regulates angiogenesis induced by colon cancer cells. Cell, 93(5), 705-16, 1998.
Chang, MS, Tsai, JC, Yang, R, DuBois, RN, Breyer, MD, O''Day, DM. Induction of rabbit cyclooxygenase 2 in the anterior uvea following glaucoma
filtration surgery. Curr Eye Res, 16(11), 1147-51, 1997.
Coffey, RJ, Hawkey, CJ, Damstrup, L, Graves-Deal, R, Daniel, VC, Dempsey, PJ, Chinery, R, Kirkland, SC, DuBois, RN, Jetton, TL, Morrow, JD. Epidermal growth factor receptor activation induces nuclear targeting of cyclooxygenase-2,
basolateral release of prostaglandins, and mitogenesis in polarizing colon cancer cells. Proc Natl Acad Sci U S A, 94(2), 657-62, 1997. PMCID:19569
DuBois, R, Tsujii, M, Morrow, J, Awad, J, Roberts, L, Bishop, P. Eicosanoid production and growth regulation in rat intestinal epithelial cells. Adv Exp Med Biol, 400A, 487-93, 1997.
Sheng, GG, Shao, J, Sheng, H, Hooton, EB, Isakson, PC, Morrow, JD, Coffey, RJ, DuBois, RN, Beauchamp, RD. A selective cyclooxygenase 2 inhibitor suppresses the growth of H-ras-transformed
rat intestinal epithelial cells. Gastroenterology, 113(6), 1883-91, 1997.
Sheng, H, Shao, J, Hooton, EB, Tsujii, M, DuBois, RN, Beauchamp, RD. Cyclooxygenase-2 induction and transforming growth factor beta growth inhibition
in rat intestinal epithelial cells. Cell Growth Differ, 8(4), 463-70, 1997.
Sheng, H, Shao, J, Kirkland, S C, Isakson, P, Coffey, R J, Morrow, J, Beauchamp, R D, DuBois, R N. Inhibition of human colon cancer cell growth by selective inhibition of cyclooxygenase-2. J Clin Invest, 99(9), 2254-9, 1997. PMCID:508057
Smith, B, DuBois, RN. Current concepts in colorectal cancer prevention. Compr Ther, 23(3), 184-9, 1997.
Tsujii M, Kuwano S, Dubois RN . Cyclooxygenase-2 Expression in Human Colon Cancer Cells Increases Metastatic Potential. Proc. Natl. Acad. Sci. USA, 94, 3336-3340, 1997.
Tsujii, M, Kawano, S, DuBois, RN. Cyclooxygenase-2 expression in human colon cancer cells increases metastatic
potential. Proc Natl Acad Sci U S A, 94(7), 3336-40, 1997. PMCID:20370
Williams, CS, Smalley, W, DuBois, RN. Aspirin use and potential mechanisms for colorectal cancer prevention. J Clin Invest, 100(6), 1325-9, 1997. PMCID:508309
Zhang, T, Nanney, LB, Luongo, C, Lamps, L, Heppner, KJ, DuBois, RN, Beauchamp, RD. Concurrent overexpression of cyclin D1 and cyclin-dependent kinase 4 (Cdk4)
in intestinal adenomas from multiple intestinal neoplasia (Min) mice and human familial adenomatous polyposis
patients. Cancer Res, 57(1), 169-75, 1997.
Zhang, T, Nanney, LB, Peeler, MO, Williams, CS, Lamps, L, Heppner, KJ, DuBois, RN, Beauchamp, RD. Decreased transforming growth factor beta type II receptor expression in intestinal
adenomas from Min/+ mice is associated with increased cyclin D1 and cyclin-dependent kinase 4 expression. Cancer Res, 57(9), 1638-43, 1997.
DuBois RN, Shao J, Sheng H, Tsujii M and Beauchamp RD. G1 Delay in Intestinal Epithelial Cells Overexpressing Prostaglandin Endoperoxide Synthase-2. Cancer Res., 56, 733-737, 1996.
DuBois, RN, Eberhart, CF, Williams, CS. Introduction to eicosanoids and the gastroenteric tract. Gastroenterol Clin North Am, 25(2), 267-77, 1996.
DuBois, RN, Radhika, A, Reddy, BS, Entingh, AJ. Increased cyclooxygenase-2 levels in carcinogen-induced rat colonic tumors. Gastroenterology, 110(4), 1259-62, 1996.
DuBois, RN, Shao, J, Tsujii, M, Sheng, H, Beauchamp, RD. G1 delay in cells overexpressing prostaglandin endoperoxide synthase-2. Cancer Res, 56(4), 733-7, 1996.
Dubois RN, Radhika A, Reddy BS and Entingh AJ. Increases Cyclooxygenase-2 Levels in Carcinogen-Induced Rat Colonic Tumors. Gastroenterology, 110, 1259-1262, 1996.
Williams CS, Luongo C, Radhika A, Zhang T, Lamps LW, Nanney LB, Beauchamp RD and DuBois RN. Elevated Cyclooxygenase-2 Levels in Min Mouse Adenomas. Gastroenterology, 111, 1134-1140, 1996.
Williams, CS, DuBois, RN. Prostaglandin endoperoxide synthase: why two isoforms. Am J Physiol, 270(3 Pt 1), G393-400, 1996.
Williams, CS, Luongo, C, Radhika, A, Zhang, T, Lamps, LW, Nanney, LB, Beauchamp, RD, DuBois, RN. Elevated cyclooxygenase-2 levels in Min mouse adenomas. Gastroenterology, 111(4), 1134-40, 1996.
Barnard, JA, Beauchamp, RD, Russell, WE, Dubois, RN, Coffey, RJ. Epidermal growth factor-related peptides and their relevance to gastrointestinal
pathophysiology. Gastroenterology, 108(2), 564-80, 1995.
Capdevila, JH, Morrow, JD, Belosludtsev, YY, Beauchamp, DR, DuBois, RN, Falck, JR. The catalytic outcomes of the constitutive and the mitogen inducible isoforms
of prostaglandin H2 synthase are markedly affected by glutathione and glutathione peroxidase(s). Biochemistry, 34(10), 3325-37, 1995.
DuBois, RN, Bishop, PR, Graves-Deal, R, Coffey, RJ. Transforming growth factor alpha regulation of two zinc finger-containing immediate
early response genes in intestine. Cell Growth Differ, 6(5), 523-9, 1995.
Eberhart, CE, Dubois, RN. Eicosanoids and the gastrointestinal tract. Gastroenterology, 109(1), 285-301, 1995.
Tsujii, M, DuBois, R N. Alterations in cellular adhesion and apoptosis in epithelial cells overexpressing prostaglandin endoperoxide synthase 2. Cell, 83(3), 493-501, 1995.
Zeldin, DC, DuBois, RN, Falck, JR, Capdevila, JH. Molecular cloning, expression and characterization of an endogenous human cytochrome
P450 arachidonic acid epoxygenase isoform. Arch Biochem Biophys, 322(1), 76-86, 1995.
Barnard, JA, Graves-Deal, R, Pittelkow, MR, DuBois, R, Cook, P, Ramsey, GW, Bishop, PR, Damstrup, L, Coffey, RJ. Auto- and cross-induction within the mammalian epidermal growth factor-related
peptide family. J Biol Chem, 269(36), 22817-22, 1994.
DuBois RN, Tsujii M, Bishop P, Awad JA, Makita K & Lanahan A. Cloning & Characterization of a Growth Factor Inducible Cyclooxygenase Gene from Rat Intestinal Epithelial Cells. Am. J. Physiol., 226, G6822-G6817, 1994.
DuBois, RN. Can we prevent colorectal cancer. Dig Dis, 12(5), 255-8, 1994.
DuBois, RN. Activin A and hepatocyte growth regulation. Hepatology, 19(3), 788-90, 1994.
DuBois, RN, Awad, J, Morrow, J, Roberts, LJ, Bishop, PR. Regulation of eicosanoid production and mitogenesis in rat intestinal epithelial
cells by transforming growth factor-alpha and phorbol ester. J Clin Invest, 93(2), 493-8, 1994. PMCID:293869
DuBois, RN, Tsujii, M, Bishop, P, Awad, JA, Makita, K, Lanahan, A. Cloning and characterization of a growth factor-inducible cyclooxygenase gene
from rat intestinal epithelial cells. Am J Physiol, 266(5 Pt 1), G822-7, 1994.
Eberhart CE, Coffey RJ, Radhika A, Giardiello FM, Ferrenbach S, and Dubois RN. Upregulation of Cyclooxygenase-2 Gene Expression in Human Colorectal Ademonas and Ademocarcinomas. Gastroenterology, 107, 1183-1188, 1994.
Eberhart, CE, Coffey, RJ, Radhika, A, Giardiello, FM, Ferrenbach, S, DuBois, RN. Up-regulation of cyclooxygenase 2 gene expression in human colorectal adenomas
and adenocarcinomas. Gastroenterology, 107(4), 1183-8, 1994.
Harris, RC, McKanna, JA, Akai, Y, Jacobson, HR, Dubois, RN, Breyer, MD. Cyclooxygenase-2 is associated with the macula densa of rat kidney and increases
with salt restriction. J Clin Invest, 94(6), 2504-10, 1994. PMCID:330084
Collins, JF, Honda, T, Knobel, S, Bulus, NM, Conary, J, DuBois, R, Ghishan, FK. Molecular cloning, sequencing, tissue distribution, and functional expression
of a Na+/H+ exchanger (NHE-2). Proc Natl Acad Sci U S A, 90(9), 3938-42, 1993. PMCID:46421
Karara, A, Makita, K, Jacobson, HR, Falck, JR, Guengerich, FP, DuBois, RN, Capdevila, JH. Molecular cloning, expression, and enzymatic characterization of the rat kidney
cytochrome P-450 arachidonic acid epoxygenase. J Biol Chem, 268(18), 13565-70, 1993.
Capdevila, JH, Wei, S, Yan, J, Karara, A, Jacobson, HR, Falck, JR, Guengerich, FP, DuBois, RN. Cytochrome P-450 arachidonic acid epoxygenase. Regulatory control of the renal
epoxygenase by dietary salt loading. J Biol Chem, 267(30), 21720-6, 1992.
Vanderbilt University is committed to principles of equal opportunity and affirmative action.
Copyright © 2008 Vanderbilt University School of Medicine
The office of Biomedical Research Education & Training All rights reserved.
For questions or problems concerning this page, please submit a help ticket.