Open AccessCritical role for constitutive type I interferon signaling in the prevention of cellular transformation
Author(s) -
Chen Huimin,
Tanaka Nobuyuki,
Mitani Yukiko,
Oda Eri,
Nozawa Hiroaki,
Chen Jianzhong,
Yanai Hideyuki,
Negishi Hideo,
Choi Myoung Kwon,
Iwasaki Toshiroh,
Yamamoto Hiroyuki,
Taniguchi Tadatsugu,
Takaoka Akinori
Publication year - 2009
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2008.01051.x
Subject(s) - biology , interferon type i , signal transduction , alpha interferon , interferon , receptor , microbiology and biotechnology , beta (programming language) , transformation (genetics) , cancer research , alpha (finance) , immunology , gene , genetics , medicine , construct validity , nursing , patient satisfaction , computer science , programming language
Interferons‐α/β, which are produced upon viral infection, are key soluble factors for the establishment of an antiviral state, but are also produced at low levels in the absence of infection. Herein, we demonstrate that a weak signal by these constitutively produced IFN‐α/β show a preventive role in cellular transformation. Ifnar1 ‐deficient ( Ifnar1 −/– ) MEF, which are devoid of IFN‐α/β signal, undergo a spontaneous transformation during long‐term cell culture. Similar to Irf1 −/– MEF, primary Ifnar1 −/– MEF become tumorigenic in nude mice by the expression of activated c‐Ha‐Ras oncoprotein. However, Ifnar1 −/– MEF do not show any abnormal growth properties. A similar observation is made in Ifnb −/– MEF that fail to produce constitutive IFN‐α/β, whereas such a transforming property is not found in MEF that lack any of the IFN receptor downstream molecules including Stat1, IRF9 and IRF1. Furthermore, Ifnar1 −/– mice develop chemically‐induced skin papilloma more severely than wild‐type mice. In addition, the expression levels of IFNAR1 mRNA are significantly decreased in human gastric cancer tissues. These results suggest a cell‐intrinsic role of the weak signal by constitutively produced IFN‐α/β to prevent cells from transformation, which may be mediated by a hitherto‐unknown pathway(s) downstream of the IFN‐α/β receptor. ( Cancer Sci 2009; 100: 449–456)