Type I interferon prolongs cell cycle progression via p21WAF1/CIP1 induction in human colon cancer cells.
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-alpha and IFN-beta 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-alpha2b and IFN-beta 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 p21WAF1/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-alpha2b and IFN-beta 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.
Department of General Surgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan. tomonari@f4.dion.ne.jp
Tomonari
T
Katayama
Kazuaki
K
Nakanishi
Hiroshi
H
Nishihara
Naoya
N
Kamiyama
Takahito
T
Nakagawa
Toshiya
T
Kamiyama
Ken
K
Iseki
Shinya
S
Tanaka
Satoru
S
Todo
D017209:Apoptosis; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism / Q000502:physiology*; D018450:Disease Progression; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007370:Interferon Type I / Q000378:metabolism*; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology; D016899:Interferon-beta / Q000494:pharmacology; D034622:RNA Interference; D011994:Recombinant Proteins; D016196:S Phase
D050759:Cyclin-Dependent Kinase Inhibitor p21; D004791:Enzyme Inhibitors; D007370:Interferon Type I; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D016899:Interferon-beta