Aberrant expression of interferon regulatory factor 3 in human lung cancer.
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.
Tokunaga
Takayuki
T
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.
Naruke
Yuki
Y
Shigematsu
Sayuri
S
Kohno
Tomoko
T
Yasui
Kiyoshi
K
Ma
Yuhua
Y
Chua
Koon Jiew
KJ
Katayama
Ikuo
I
Nakamura
Takashi
T
Hishikawa
Yoshitaka
Y
Koji
Takehiko
T
Yatabe
Yasushi
Y
Nagayasu
Takeshi
T
Fujita
Takashi
T
Matsuyama
Toshifumi
T
Hayashi
Hideki
H
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
C494232:IRF3 protein, human; D050838:Interferon Regulatory Factor-3