Overexpression of cyclin DI contributes to malignant properties of esophageal tumor cells by increasing VEGF production and decreasing Fas expression

Masafum Shintani, Aki Okazaki, Tohru Masuda, Manabu Kawada, Masaaki Ishizuka, Yuichiro Doki, I. Bernard Weinstein, Masaya Imoto

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Cyclin D1 is frequently overexpressed in human esophageal cancer. We examined the possible role of cyclin D1 overexpression on specific malignant properties of tumor cells using a series of eight human esophageal cancer cell lines that express different levels of cyclin D1. We did not find a simple correlation between levels of cyclin D1 expression and anchorage-independent growth, production of angiogenic factors, or tumorigenicity in nude mice, suggesting that other factors can influence these parameters. We did, however, obtain evidence that tumorigenicity appeared to require both the capacity for anchorage-independent growth and the production of angiogenic factors. To better assess the specific role of cyclin D1, we stably expressed an antisense cyclin D1 cDNA construct in the tumorigenic cell line TTn. This significantly decreased anchorage-independent growth and VEGF production and led to a loss of tumorigenicity in nude mice. Furthermore, these cells diplayed a marked increase in sensitivity to antitumor agents and to Fas antibody-induced apoptosis. Taken together, these findings suggest that the overexpression of cyclin D1 can confer esophageal cancer cells with enhanced malignancy through increases in anchorage-independent growth and VEGF production, and down-regulation of Fas expression, thus suggesting novel functions of the cyclin D1 protein in tumor progression.

Original languageEnglish
Pages (from-to)639-647
Number of pages9
JournalAnticancer research
Volume22
Issue number2 A
Publication statusPublished - 2002 May 16

Keywords

  • Cyclin D1
  • Esophageal tumor
  • Fas
  • VEGF

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Shintani, M., Okazaki, A., Masuda, T., Kawada, M., Ishizuka, M., Doki, Y., Weinstein, I. B., & Imoto, M. (2002). Overexpression of cyclin DI contributes to malignant properties of esophageal tumor cells by increasing VEGF production and decreasing Fas expression. Anticancer research, 22(2 A), 639-647.