Abstract
Recent epidemiological and experimental investigations suggest a close relationship between cyclooxygenase (COX) and pathogenesis of colorectal cancer.’ There are two isoforms, COX-1 and COX-2, which differ in physiological functions and distribution.2,3This study is to investigate the possible roles of both isoforms in the proliferation of colon carcinoma cells. A human colon carcinoma cell line, COLO 320DM, was transfected with an eukaryotic expression vector (pEF-BOS) carrying cDNA of either COX-1 or COX-2. Both COX-1 and COX-2-expressing cells exhibited a similar enzyme activity, 8-10 nmol/10 min/mg of protein. Growth rates of both COX-expressing cells were increased by about 2 fold as compared with mock-transfected cells. The stimulated growth of the COX-expressing cells was confirmed by the increased DNA synthesis as assessed by [3H]thymidine incorporation. Furthermore, expression of epidermal growth factor receptor (EGFR) was markedly increased in the COX-expressing cells as examined by reverse transcriptase-polymerase chain reaction (RT-PCR). A COX inhibitor, indomethacin, suppressed the stimulated growth, increased DNA synthesis and induction of epidermal growth factor receptor in the COX-1 and COX-2-transfected cells. These results suggest that not only COX-2 but COX-1 is involved in the proliferation of human colon carcinoma cells through the induction of EGFR.
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References
R.N. Dubois, S.B. Abramson, L. Crofford, R.A. Gupta, L.S. Simon, L.B.A. Van De Putte and P.E. Lipsky, Cyclooxygenase in biology and diseaseFASEB J.12:1063 (1998).
W.L. Smith, R.M. Garavito, and D.L. DeWitt, Prostaglandin endoperoxide H synthases (cyclooxygenases) -1 and -2J. Biol. Chem.271: 33157 (1996).
J.R. Vane, Y.S. Bakhle, and R.M. Botting, Cyclooxygenase 1 and 2Annu. Rev. Pharmacol. Toxicol.38: 97 (1998).
S. Mizushima and S. Nagata, pEF-BOS, a powerful mammalian expression vectorNucleic Acids Res.18: 5322 (1990).
D. Hwang, D. Scollard, J. Byrne, and E. Levine, Expression of cyclooxygenase-1 and cyclooxygenase-2 in human breast cancerJ. Natl. Cancer Inst.90: 455 (1998).
M. Dore, L.C. Cote, A. Mitchell, and J. Sirois, Expression of prostaglandin G/H synthase type 1, but not type 2, in human ovarian adenocarcinomasJ. Histochem. Cytochem.46: 77 (1998).
C.E. Eberhart, R.J. Coffey, A. Radhika, F.M. Giardiello, S. Ferrenbach, and R.N. DuBois, Up-regulation of cyclooxygenase 2 gene expression in human colorectal adenomas and adenocarcinomasGastroenterology107: 1183 (1994).
H. Sano, Y. Kawahito, R.L. Wilder, A. Hashiramoto, S. Mukai, K. Asai, S. Kimura, H. Kato, M. Kondo, and T. Hla, Expression of cyclooxygenase-1 and -2 in human colorectal cancerCancer Res.55: 3785 (1995).
S.L. Kargman, G.P. O’Neill, P.J. Vickers, J.F. Evans, J.A. Mancini, and S. Jothy, Expression of prostaglandin G/H synthase-1 and -2 protein in human colon cancerCancer Res.55: 2556 (1995).
L. Kaplan, J. Weiss, and P. Elsbach, Low concentrations of indomethacin inhibit phospholipase A2 of rabbit polymorphonuclear leukocytesProc. Natl. Acad. Sci. USA75: 2955 (1978).
J.M. Lehmann, J.M. Lenhard, B.B. Oliver, G.M. Ringold, and S.A. Kliewer, Peroxisome proliferatoractivated receptors a and gare activated by indomethacin and other non-steroidal anti-inflammatory drugsJ. Biol. Chem.272: 3406 (1997).
G. Carpenter, and S. Cohen, Epidermal growth factorJ. Biol. Chem.265: 7709 (1990).
M. Bos, J. Mendelsohn, Y-H. Kim, J. Albanell, D.W. Fry, and J. Baselga, PD153035, a tyrosine kinase inhibitor, prevents epidermal growth factor receptor activation and inhibits growth of cancer cells in a receptor number-dependent mannerClin. Cancer Res.3: 2099 (1997).
J.D. Moyer, E.G. Barbacci, K.K. Iwata, L. Arnold, B. Boman, A. Cunningham, C. DiOrio, J. Doty, M.J. Morin, M.P. Moyer, M. Neveu, V.A. Pollack, L.R. Pustilnik, M.M. Reynolds, D. Sloan, A. Theleman, and P. Miller, Induction of apotosis and cell cycle arrest by CP-358, 774, an inhibitor of epidermal growth factor receptor tyrosine kinaseCancer Res.57: 4838 (1997).
X. Wu, Z. Fan, H. Masui, N. Rosen, and J. Mendelsohn, Apotosis induced by an anti-epidermal growth factor receptor monoclonal antibody in human colorectal carcinoma cell line and its delay by insulinJ. Clin. Invest.95: 1897 (1995).
S.D. Markowitz, K. Molkentin, C. Gerbic, J. Jackson, T. Stellato, and J.K.V. Willson, Growth stimulation by coexpression of transforming growth factor-a and epidermal growth factor-receptor in normal and adenomatous human colon epitheliumJ. Clin. Invest.86: 356 (1990).
R.J. Coffey, C.J. Hawkey, L. Damstrup, R. Graves-Deal, V.C. Daniel, P.J. Dempsey, R. Chinery, S.C. Kirkland, R.N. DuBois, T.J. Jetton, and J.D. Morrow, Epidermal growth factor receptor activation induces nuclear targeting of cyclooxygenase-2, basolateral release of prostaglandins, and mitogenesis in polarizing colon cancer cellsProc. Natl. Acad. Sci. USA94: 657 (1997).
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Yoshimoto, T., Takahashi, Y., Kinoshita, T., Sakashita, T., Inoue, H., Tanabe, T. (2002). Growth Stimulation and Epidermal Growth Factor Receptor Induction in Cyclooxygenase-Overexpressing Human Colon Carcinoma Cells. In: Honn, K.V., Marnett, L.J., Nigam, S., Dennis, E., Serhan, C. (eds) Eicosanoids and Other Bioactive Lipids in Cancer, Inflammation, and Radiation Injury, 5. Advances in Experimental Medicine and Biology, vol 507. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-0193-0_62
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DOI: https://doi.org/10.1007/978-1-4615-0193-0_62
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