Growth stimulation and epidermal growth factor receptor induction in cyclooxygenase-overexpressing human colon carcinoma cells.
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. This 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.
Yoshimoto
Tanihiro
T
Department of Pharmacology, Kanazawa University School of Medicine, Kanazawa 920-8640, Japan.
Takahashi
Yoshitaka
Y
Kinoshita
Takahiro
T
Sakashita
Toshiki
T
Inoue
Hiroyasu
H
Tanabe
Tadashi
T
D002455:Cell Division / Q000502:physiology*; D003110:Colonic Neoplasms; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D066246:ErbB Receptors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D007700:Kinetics; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D007527:Isoenzymes; D008565:Membrane Proteins; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D066246:ErbB Receptors