Cysteine-rich intestinal protein 2 ( CRIP2 ) acts as a repressor of NF-κB–mediated proangiogenic cytokine transcription to suppress tumorigenesis and angiogenesis
| Autor: | Daniel Chua, Josephine Mun Yee Ko, Kwok Wah Chan, Eric J. Stanbridge, Arthur Kwok Leung Cheung, Hong Lok Lung, Maria Li Lung, Dora L.W. Kwong, Eugene R. Zabarovsky, Sai Wah Tsao, Lisa Kashima, Toshiharu Suzuki, Takashi Tokino |
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| Rok vydání: | 2011 |
| Předmět: |
Antiangiogenesis
Transcription Genetic Angiogenesis medicine.medical_treatment Repressor Biology medicine.disease_cause Cell Line Cytokines - genetics - physiology chemistry.chemical_compound Cell Line Tumor medicine Humans Angiogenic Proteins Cell Transformation Neoplastic - genetics Adaptor Proteins Signal Transducing Chromosomes Human Pair 14 Adaptor Proteins Signal Transducing - physiology Neovascularization Pathologic - genetics Multidisciplinary Neovascularization Pathologic Tumor Suppressor Proteins NF-kappa B NF-kappa B - metabolism NF-κB Biological Sciences LIM Domain Proteins NFKB1 Molecular biology Repressor Proteins Cell Transformation Neoplastic Cytokine chemistry Tumor progression Cancer cell Cancer research Cytokines Transcription regulator Carcinogenesis |
| Zdroj: | Proceedings of the National Academy of Sciences. 108:8390-8395 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.1101747108 |
| Popis: | Chromosome 14 was transferred into tumorigenic nasopharyngeal carcinoma and esophageal carcinoma cell lines by a microcell-mediated chromosome transfer approach. Functional complementation of defects present in the cancer cells suppressed tumor formation. A candidate tumor-suppressor gene, cysteine-rich intestinal protein 2 (CRIP2), located in the hot spot for chromosomal loss at 14q32.3, was identified as an important candidate gene capable of functionally suppressing tumor formation. Previous studies have shown that CRIP2 is associated with development. To date, no report has provided functional evidence supporting a role for CRIP2 in tumor development. The present study provides unequivocal evidence that CRIP2 can functionally suppress tumorigenesis. CRIP2 is significantly down-regulated in nasopharyngeal carcinoma cell lines and tumors. CRIP2 reexpression functionally suppresses in vivo tumorigenesis and angiogenesis; these effects are induced by its transcription-repressor capability. It interacts with the NF-κB/p65 to inhibit its DNA-binding ability to the promoter regions of the major proangiogenesis cytokines critical for tumor progression, including IL6, IL8, and VEGF. In conclusion, we provide compelling evidence that CRIP2 acts as a transcription repressor of the NF-κB-mediated proangiogenic cytokine expression and thus functionally inhibits tumor formation and angiogenesis. link_to_OA_fulltext |
| Databáze: | OpenAIRE |
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