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Interferon regulatory factor‐2 point mutations in human pancreatic tumors
Author(s) -
Xi Hongkang,
Blanck George
Publication year - 2000
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/1097-0215(20000915)87:6<803::aid-ijc7>3.0.co;2-e
Subject(s) - ciita , irf1 , transactivation , biology , interferon regulatory factors , point mutation , interferon , transcription factor , promoter , cancer research , microbiology and biotechnology , dna binding domain , mutant , mhc class ii , gene , genetics , major histocompatibility complex , gene expression
Interferon regulatory factor (IRF)‐2, a member of the IRF family, is a transcription factor involved in the regulation of various interferon and virus‐stimulated genes and other genes. For example, IRF‐2 is an activator of the interferon (IFN)‐γ‐inducible MHC class II transactivator (CIITA) type IV promoter. It cooperates with IRF‐1 in the activation of the CIITA type IV promoter and can co‐occupy the IRF‐E of the promoter with IRF‐1. In a previous study, we identified an inactivating point mutation in the DNA binding domain of IRF‐2 expressed in a human pancreatic tumor cell line that does not express CIITA or MHC class II in response to IFN‐γ. To further assess the potential impact of IRF‐2 mutations in tumorigenesis, we screened fresh pancreatic tumor explants and identified 2 IRF‐2 point mutations in the 2 alleles of IRF‐2 from a single tumor specimen. Both mutations occurred in the DNA binding domain of IRF‐2. DNA binding assays demonstrated that the IRF‐2 point mutations impaired IRF‐2 DNA binding. The transactivation function of the mutant IRF‐2s was similarly impaired. This is the first report of IRF‐2 mutations in human tumor explants. Int. J. Cancer 87:803–808, 2000. © 2000 Wiley‐Liss, Inc.