title: Aberrant expression of interferon regulatory factor 3 in human lung cancer.
abstract: We analyzed the subcellular distributions and gene structures of interferon regulatory factor 3 (IRF3) transcription factor in 50 cases of human primary lung cancer. The immunohistochemical analyses revealed substantially aberrant IRF3 expression specific to the cancer lesions (2 and 6 tumors with nuclear staining, and 4 and 5 tumors with negative staining, in adenocarcinoma and squamous cell carcinoma, respectively), while the morphologically normal region around the tumors exhibited only cytoplasmic staining. In addition, we determined the sequence of the entire IRF3 coding region, and found two novel variants with the amino acid changes (S(175)(AGC)-->R(175)(CGC) and A(208)(GCC)-->D(208)(GAC)). The R(175) variant was also detected in a morphologically normal region around the nuclear staining squamous cell carcinoma, and exhibited almost the same functions as the wild type IRF3. On the other hand, the D(208) variant, found in the negative staining squamous cell carcinoma cases, reduced the nuclear translocation in response to IkappaB kinase epsilon stimulation, as compared to the wild type IRF3, but the same variant was detected in the surrounding morphologically normal region. The aberrant expression of IRF3 and the novel D(208) variant may provide clues to elucidate the etiology of primary lung cancer.
authors.affiliation: Division of Cytokine Signaling, Department of Molecular Microbiology and Immunology, Nagasaki University Graduate School of Biomedical Science, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Tokunaga
authors.forename: Yuki
authors.initials: Y
authors.lastname: Naruke
authors.forename: Sayuri
authors.initials: S
authors.lastname: Shigematsu
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kohno
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Yasui
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Ma
authors.forename: Koon Jiew
authors.initials: KJ
authors.lastname: Chua
authors.forename: Ikuo
authors.initials: I
authors.lastname: Katayama
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakamura
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Hishikawa
authors.forename: Takehiko
authors.initials: T
authors.lastname: Koji
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Yatabe
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nagayasu
authors.forename: Takashi
authors.initials: T
authors.lastname: Fujita
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Matsuyama
authors.forename: Hideki
authors.initials: H
authors.lastname: Hayashi
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D002460:Cell Line; D005260:Female; D006367:HeLa Cells; D006801:Humans; D050838:Interferon Regulatory Factor-3 / Q000235:genetics / Q000378:metabolism*; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D021381:Protein Transport / Q000528:radiation effects; D014965:X-Rays
chemical_list: C494232:IRF3 protein, human; D050838:Interferon Regulatory Factor-3