Adenovirus-mediated expression of dominant negative c-myb induces apoptosis in head and neck cancer cells and inhibits tumor growth in animal model
| Autor: | Myoung Ja Chung, Pyoung Han Hwang, Yun Soo Yang, Dae Yeol Lee, Kyu Yun Jang, Jung Chang Lee, Sang-Yun Nam, Sun-Young Kim, Ho Keun Yi, Ki Hwang Hong |
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| Rok vydání: | 2008 |
| Předmět: |
Male
Cancer Research animal structures Genetic enhancement Genetic Vectors Down-Regulation Mice Nude Apoptosis Gene delivery Biology Proto-Oncogene Mas Adenoviridae Mice Proto-Oncogene Proteins c-myb medicine Animals Humans Growth Substances Protein kinase B Mice Inbred BALB C Cell growth Cell Cycle fungi Gene Transfer Techniques Genetic Therapy Cell cycle medicine.disease Head and neck squamous-cell carcinoma Disease Models Animal Proto-Oncogene Proteins c-bcl-2 Oncology Head and Neck Neoplasms Immunology Carcinoma Squamous Cell Cancer research Oral Surgery Cell Division Neoplasm Transplantation |
| Zdroj: | Oral Oncology. 44:383-392 |
| ISSN: | 1368-8375 |
| DOI: | 10.1016/j.oraloncology.2007.05.004 |
| Popis: | The recent demonstration of aberrant expression of the c-myb proto-oncogene in various cancers suggests that c-myb plays an important role in the development of cancer. On this basis, it has been proposed that ablation of c-myb function might be an effective approach for therapy of c-myb dependent malignancies. We previously used a dominant negative c-myb (DN-myb) construct to induce apoptosis in K562 cells. In this study, DN-myb was expressed in an adenovirus-mediated gene delivery system and introduced into head and neck squamous cell carcinoma cells (HNSCC) in vitro and in vivo to examine its tumor suppressive function and its potential in HNSCC gene therapy. Over expression of DN-myb in HNSCC cells inhibited in vitro cell proliferation, expression of growth factors such as IGF-I, -II, IGF-1R, and VEGF, inhibited Akt/PKB pathway activation, and enhanced induction of apoptosis. Similarly, in vivo administration of DN-myb retarded tumor-growth. Our results support a role for DN-myb in inducing apoptosis and tumor suppression, and, furthermore, suggest that DN-myb gene therapy might provide a powerful tool for treatment of c-myb dependent malignancies such as HNSCC. |
| Databáze: | OpenAIRE |
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