Hepatocyte growth factor induces anoikis resistance by up-regulation of cyclooxygenase-2 expression in uterine endometrial cancer cells

  • Authors:
    • Seiji Kanayama
    • Yoshihiko Yamada
    • Ryuji Kawaguchi
    • Yoriko Tsuji
    • Shoji Haruta
    • Hiroshi Kobayashi
  • View Affiliations

  • Published online on: January 1, 2008     https://doi.org/10.3892/or.19.1.117
  • Pages: 117-122
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Abstract

Cyclooxygenase-2 (COX-2) has been implicated in the promotion of carcinogenesis. Although the role of COX-2 in endometrial cancer remains unclear, recent experiments suggest that COX-2 antagonizes cell apoptosis, increases the invasiveness of malignant cells, and promotes angiogenesis. Hepatocyte growth factor (HGF) is a mesenchymal-derived cytokine and the interaction between HGF and its tyrosine kinase receptor, c-Met proto-oncogene, is associated with tumor progression and metastasis. To investigate the molecular mechanism of HGF-induced anoikis resistance, we analyzed the signal transduction and COX-2 expression in endometrial cancer cells. Here, we show i) the expression of COX-2 protein significantly increased in a dose-dependent manner after HGF stimulation in endometrial cancer cell lines (HEC-IB and RL95-2), reaching 200-270% stimulation at the highest doses of HGF tested (40 ng/ml); ii) flow cytometry and TUNEL analyses revealed that HGF significantly inhibited anoikis of RL95-2 cells; iii) phosphatidylinositol 3-kinase (PI3K) inhibitor (LY294002), but not mitogen-activated protein kinase/ERK kinase (MEK) inhibitor (PD98059), specifically blocked HGF-mediated anoikis resistance in RL95-2 cells; and iv) COX-2 inhibitor, Meloxicam, abrogated HGF-mediated anoikis resistance. Our data suggest that HGF induces anoikis resistance in endometrial cancer cells possibly through PI3K/Akt pathway-dependent up-regulation of COX-2 expression.

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January 2008
Volume 19 Issue 1

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Kanayama S, Yamada Y, Kawaguchi R, Tsuji Y, Haruta S and Kobayashi H: Hepatocyte growth factor induces anoikis resistance by up-regulation of cyclooxygenase-2 expression in uterine endometrial cancer cells. Oncol Rep 19: 117-122, 2008.
APA
Kanayama, S., Yamada, Y., Kawaguchi, R., Tsuji, Y., Haruta, S., & Kobayashi, H. (2008). Hepatocyte growth factor induces anoikis resistance by up-regulation of cyclooxygenase-2 expression in uterine endometrial cancer cells. Oncology Reports, 19, 117-122. https://doi.org/10.3892/or.19.1.117
MLA
Kanayama, S., Yamada, Y., Kawaguchi, R., Tsuji, Y., Haruta, S., Kobayashi, H."Hepatocyte growth factor induces anoikis resistance by up-regulation of cyclooxygenase-2 expression in uterine endometrial cancer cells". Oncology Reports 19.1 (2008): 117-122.
Chicago
Kanayama, S., Yamada, Y., Kawaguchi, R., Tsuji, Y., Haruta, S., Kobayashi, H."Hepatocyte growth factor induces anoikis resistance by up-regulation of cyclooxygenase-2 expression in uterine endometrial cancer cells". Oncology Reports 19, no. 1 (2008): 117-122. https://doi.org/10.3892/or.19.1.117