Overexpressed NF-kappaB-inducing kinase contributes to the tumorigenesis of adult T-cell leukemia and Hodgkin Reed-Sternberg cells
| Autor: | Takao Masuda, Naoki Yamamoto, Haruyo Sugimoto, Atae Utsunomiya, Yasunori Saitoh, Shoji Yamaoka, Xiaohua Qi, Johji Inazawa, Katsuyoshi Matsubara, Vicente Javier Martínez Bruyn, M. Zahidunnabi Dewan, Issei Imoto, Norio Yamamoto, Toshiki Watanabe, Tatsuya Saitoh, Yuki Iwasaki |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Immunology
T-cell leukemia Cell Biology Protein Serine-Threonine Kinases medicine.disease_cause Biochemistry Mice RNA interference hemic and lymphatic diseases medicine Animals Leukemia-Lymphoma Adult T-Cell RNA Small Interfering Reed-Sternberg Cells Transcription factor Kinase NF-kappa B Cell Biology Hematology Hodgkin Disease Rats Gene Expression Regulation Neoplastic IκBα medicine.anatomical_structure Cell Transformation Neoplastic Cancer cell Cancer research Carcinogenesis |
| Zdroj: | Blood. 111(10) |
| ISSN: | 1528-0020 |
| Popis: | The nuclear factor-κB (NF-κB) transcription factors play important roles in cancer development by preventing apoptosis and facilitating the tumor cell growth. However, the precise mechanisms by which NF-κB is constitutively activated in specific cancer cells remain largely unknown. In our current study, we now report that NF-κB–inducing kinase (NIK) is overexpressed at the pretranslational level in adult T-cell leukemia (ATL) and Hodgkin Reed-Sternberg cells (H-RS) that do not express viral regulatory proteins. The overexpression of NIK causes cell transformation in rat fibroblasts, which is abolished by a super-repressor form of IκBα. Notably, depletion of NIK in ATL cells by RNA interference reduces the DNA-binding activity of NF-κB and NF-κB–dependent transcriptional activity, and efficiently suppresses tumor growth in NOD/SCID/γcnull mice. These results indicate that the deregulated expression of NIK plays a critical role in constitutive NF-κB activation in ATL and H-RS cells, and suggest also that NIK is an attractive molecular target for cancer therapy. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|