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Effects of epidermal growth factor(EGF) on invasive and metastatic ability of tumor cells. Part 2: Mechanisms of malignant phenotype acquisition by long-term EGF treatment.

  • NAGAYASU Hiroki
    Second Department of Oral Surgery, School of Dentistry, Health Sciences University of Hokkaido
  • SHIBATA Toshiyuki
    Second Department of Oral Surgery, School of Dentistry, Health Sciences University of Hokkaido
  • ARISUE Makoto
    Second Department of Oral Surgery, School of Dentistry, Health Sciences University of Hokkaido
  • KAWANO Takashi
    Second Department of Oral Surgery, School of Dentistry, Health Sciences University of Hokkaido
  • KATO Motoyasu
    Second Department of Oral Surgery, School of Dentistry, Health Sciences University of Hokkaido
  • NAKAI Kazumoto
    Second Department of Oral Surgery, School of Dentistry, Health Sciences University of Hokkaido
  • NAKATA Daichi
    Second Department of Oral Surgery, School of Dentistry, Health Sciences University of Hokkaido
  • KONISHI Akira
    First Department of Oral Surgery, School of Dentistry, Health Sciences University of Hokkaido
  • OKUMURA Kazuhiko
    First Department of Oral Surgery, School of Dentistry, Health Sciences University of Hokkaido

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Other Title
  • 上皮成長因子EGFが癌細胞の浸潤,転移能に及ぼす影響 第2報 EGF長期間処理による悪性形質獲得機序の検討
  • Part 2: Mechanisms of malignant phenotype acquisition by long-term EGF treatment
  • 第2報, EGF長期間処理による悪性形質獲得機序の検討

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Abstract

We have previously reported that epidermal growth factor (EGF) enhanced the invasive and metastatic abilities of regressor ER-1 cells and that ER-1 cells might acquire stable malignant phenotypes after long-term EGF treatment. In this study, we studied the mechanisms of the malignant phenotype acquisition by long-term EGF treatment.<BR>EGF enhanced the chemotactic response of ER-1 cells toward culture supernatant conditioned with rat lung endothelial cells in a dose-dependent fashion and also enhanced invasiveness into the reconstituted basement membrane (MatrigelTM) in a similar manner. Furthermore, when ER-1 cells were cultured in the presence of EGF for a month (1M EGF ER-1), they acquired stable invasiveness. In EGF binding assay using 125I-EGF, the numbers of EGF receptors were similar for ER-1 cells and 1 M EGF ER-1 cells, which expressed both highand low-affinity receptors. RT-PCR analysis demonstrated that mRNA expression of EGF receptors was similar for both ER-1 cells and 1M EGF ER-1 cells. Drug-resistance tests using c-SST-2 cells (parent cells of ER-1) revealed that colonies resistant to 6-thioguanine and ouabain appeared after long-term EGF treatment (one month).<BR>These results suggest that long-term EGF treatment may affect the genomic alteration of ER-1 cells and that these may acquire stable malignant phenotypes

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