Aberrant expression of interferon regulatory factor 3 in human lung cancer

作者：Tokunaga Takayuki; Naruke Yuki; Shigematsu Sayuri; Kohno Tomoko; Yasui Kiyoshi; Ma Yuhua; Chua Koon Jiew; Katayama Ikuo; Nakamura Takashi; Hishikawa Yoshitaka; Koji Takehiko; Yatabe Yasushi; Nagayasu Takeshi; Fujita Takashi; Matsuyama Toshifumi^*; Hayashi Hideki

来源：Biochemical and Biophysical Research Communications, 2010, 397(2): 202-207.

DOI：10.1016/j.bbrc.2010.05.085

• Interferon regulatory factor 3 (IRF3)
• Lung cancer
• Immunohistochemistry
• I kappa B kinase epsilon (IKK epsilon)

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)(GC) and A(208)(GCC) -> D(208)(GAC)). The R175 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 D208 variant, found in the negative staining squamous cell carcinoma cases, reduced the nuclear translocation in response to I kappa B 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.

• 出版日期2010-6-25