Open AccessOverexpression of the DNA sensor proteins, absent in melanoma 2 and interferon‐inducible 16, contributes to tumorigenesis of oral squamous cell carcinoma with p53 inactivation
Author(s) -
Kondo Yuudai,
Nagai Kentaro,
Nakahata Shingo,
Saito Yusuke,
Ichikawa Tomonaga,
Suekane Akira,
Taki Tomohiko,
Iwakawa Reika,
Enari Masato,
Taniwaki Masafumi,
Yokota Jun,
Sakoda Sumio,
Morishita Kazuhiro
Publication year - 2012
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.1349-7006.2012.02211.x
Subject(s) - biology , carcinogenesis , aim2 , cancer research , cell growth , microbiology and biotechnology , gene knockdown , enhancer , cell culture , gene expression , gene , innate immune system , immunology , genetics , immune system
The development of oral squamous cell carcinoma ( OSCC ) is a multistep process that requires the accumulation of genetic alterations. To identify genes responsible for OSCC development, we performed high‐density single nucleotide polymorphism array analysis and genome‐wide gene expression profiling on OSCC tumors. These analyses indicated that the absent in melanoma 2 ( AIM2 ) gene and the interferon‐inducible gene 16 ( IFI16 ) mapped to the hematopoietic interferon‐inducible nuclear proteins. The 200‐amino‐acid repeat gene cluster in the amplified region of chromosome 1q23 is overexpressed in OSCC . Both AIM2 and IFI16 are cytoplasmic double‐stranded DNA sensors for innate immunity and act as tumor suppressors in several human cancers. Knockdown of AIM2 or IFI16 in OSCC cells results in the suppression of cell growth and apoptosis, accompanied by the downregulation of nuclear factor kappa‐light‐chain‐enhancer of activated B cells activation. Because all OSCC cell lines have reduced p53 activity, wild‐type p53 was introduced in p53‐deficient OSCC cells. The expression of wild‐type p53 suppressed cell growth and induced apoptosis via suppression of nuclear factor kappa‐light‐chain‐enhancer of activated B cells activity. Finally, the co‐expression of AIM 2 and IFI 16 significantly enhanced cell growth in p53‐deficient cells; in contrast, the expression of AIM 2 and/or IFI 16 in cells bearing wild‐type p53 suppressed cell growth. Moreover, AIM 2 and IFI 16 synergistically enhanced nuclear factor kappa‐light‐chain‐enhancer of activated B cells signaling in p53‐deficient cells. Thus, expression of AIM 2 and IFI1 6 may have oncogenic activities in the OSCC cells that have inactivated the p53 system. ( Cancer Sci 2012; 103: 782–790)