Aberrant expression of interferon regulatory factor 3 in human lung cancer

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• 作者：Takayuki Tokunaga ; Yuki Naruke ; Sayuri Shigematsu ; Tomoko Kohno ; Kiyoshi Yasui ; Yuhua Ma ; Koon Jiew Chua ; Ikuo Katayama ; Takashi Nakamura ; Yoshitaka Hishikawa ; Takehiko Koji ; Yasushi Yatabe ; Takeshi N
• 关键词：Interferon regulatory factor 3 (IRF3) ; Lung cancer ; Immunohistochemistry ; Iκ ; B kinase ε ; (IKKε ; )
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2010
• 出版时间：25 June 2010
• 年：2010
• 卷：397
• 期：2
• 页码：202-207
• 全文大小：732 K

文摘

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 (S¹⁷⁵(AGC) → R¹⁷⁵(CGC) and A²⁰⁸(GCC) → D²⁰⁸(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 IκB kinase ε 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 D²⁰⁸ variant may provide clues to elucidate the etiology of primary lung cancer.