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Growth Stimulation and Epidermal Growth Factor Receptor Induction in Cyclooxygenase-Overexpressing Human Colon Carcinoma Cells

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Eicosanoids and Other Bioactive Lipids in Cancer, Inflammation, and Radiation Injury, 5

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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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

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-4960-0

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