Epigenetic inactivation of RASSF2 in oral squamous cell carcinoma
| Autor: | Hiroaki Mita, Kazuhiro Ogi, Kimishige Akino, Fumio Itoh, Yasuhisa Shinomura, Hiromu Suzuki, Hiroyoshi Hiratsuka, Reo Maruyama, Lisa Kashima, Takashi Imai, Masanori Nojima, Yohei Sogabe, Yasushi Sasaki, Minoru Toyota, Kohzoh Imai, Takashi Tokino |
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| Rok vydání: | 2008 |
| Předmět: |
Cancer Research
Apoptosis Biology medicine.disease_cause Epigenesis Genetic Cell Line Tumor medicine Humans Epigenetics Gene Cell growth Tumor Suppressor Proteins Cancer Proteins General Medicine Methylation DNA Methylation medicine.disease Immunohistochemistry stomatognathic diseases Oncology DNA methylation Immunology Cancer research Carcinoma Squamous Cell Ectopic expression Mouth Neoplasms Carcinogenesis |
| Zdroj: | Cancer science. 99(5) |
| ISSN: | 1349-7006 |
| Popis: | Genetic and epigenetic alterations in tumor-suppressor genes play important roles in human neoplasia. Ras signaling is often activated in oral squamous cell carcinoma (OSCC), although Ras mutations are rarely detected in Japanese OSCC patients, and the mechanisms underlying the gene's activation remain unclear. Here, we examined the expression of Ras association family (RASSF) genes in a panel of OSCC cell lines and found that RASSF2 is often downregulated by DNA methylation in OSCC cells. In addition, aberrant methylation of RASSF2 was detected in 12 of 46 (26%) primary OSCC, and 18 (39%) of those OSCC showed methylation of at least one RASSF gene. Ectopic expression of RASSF2 in OSCC cells suppressed cell growth and induced apoptosis. A RASSF2 deletion mutant lacking the Ras-association domain, which was therefore unable to interact with Ras, exhibited less pro-apoptotic activity than the full-length protein, indicating that the pro-apoptotic activity of RASSF2 is related to its association with Ras. Genomic screening of genes regulated by RASSF2 showed that genes involved in immune responses, angiogenesis, and metastasis are suppressed by RASSF2. Our results suggest that epigenetic inactivation of RASSF2 plays an important role in OSCC tumorigenesis, and that RASSF2 may be a useful molecular target for the diagnosis and treatment of OSCC. |
| Databáze: | OpenAIRE |
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