Type I interferon prolongs cell cycle progression via p21 WAF1/CIP1 induction in human colon cancer cells

Tomonari Katayama, Kazuaki Nakanishi, Hiroshi Nishihara, Naoya Kamiyama, Takahito Nakagawa, Toshiya Kamiyama, Ken Iseki, Shinya Tanaka, Satoru Todo

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20 Citations (Scopus)

Abstract

Type I interferon (IFN) was originally identified as an immunomodulatory cytokine because of its antiviral activity. Further characterization of its biological effects revealed a prominent role in the direct control of cell growth and potent immunomodulatory and antiangiogenic actions. IFN-α and IFN-β had both been classified as type I IFN, but differences in their antitumor activities were reported. We confirmed the difference in the antiproliferative activities of IFN-α2b and IFN-β toward HT29 and SW480 cells. IFN treatment was observed to prolong cell cycle progression; in particular, the accumulation of S-phase population was one of the most characteristic changes. The prolongation of S-phase progression and transition into G2/M-phase was suggested to be a crucial action of type I IFN on colon cancer. Additionally, IFN activated the p21 promoter gene and induced p21 WAF1/CIP1 expression. Furthermore, the cell cycle prolongation effect of IFN was suppressed when p21 expression was downregulated. Therefore, we confirmed that p21WAF1/CIP1 was a crucial target molecule for the effects of IFN on the cell cycle. Additionally, the ability of p21 induction differed between IFN-α2b and IFN-β and correlated with their inhibitory activities toward cell growth. We conclude that type I IFN prolongs cell cycle progression by p21WAF1/CIP1 induction in human colon cancer cells.

Original languageEnglish
Pages (from-to)613-620
Number of pages8
JournalInternational journal of oncology
Volume31
Issue number3
Publication statusPublished - 2007 Sep 1

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Keywords

  • Cell cycle
  • Interferon
  • p21

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Katayama, T., Nakanishi, K., Nishihara, H., Kamiyama, N., Nakagawa, T., Kamiyama, T., Iseki, K., Tanaka, S., & Todo, S. (2007). Type I interferon prolongs cell cycle progression via p21 WAF1/CIP1 induction in human colon cancer cells. International journal of oncology, 31(3), 613-620.