DNA Double-strand Break Signaling Is a Therapeutic Target in Head and Neck Cancer
| Autor: | Caryn E. Peterson, Ardaman Shergill, David L. Crowe, Kate Jillian Galvan, Ryan D. Bogard, Jianchun Wu |
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| Rok vydání: | 2021 |
| Předmět: |
Male
Cancer Research medicine.medical_treatment Mice Nude Antineoplastic Agents Apoptosis Cell Cycle Proteins Ataxia Telangiectasia Mutated Proteins Targeted therapy chemistry.chemical_compound Western blot Cell Line Tumor medicine Animals Humans DNA Breaks Double-Stranded Protein Kinase Inhibitors Cell Proliferation Regulation of gene expression medicine.diagnostic_test Kinase General Medicine Xenograft Model Antitumor Assays Tumor Burden G2 Phase Cell Cycle Checkpoints Oncology chemistry Head and Neck Neoplasms Cell culture Cancer research Immunohistochemistry Female Tumor Suppressor p53-Binding Protein 1 DNA Signal Transduction |
| Zdroj: | Anticancer Research. 41:5393-5403 |
| ISSN: | 1791-7530 0250-7005 |
| DOI: | 10.21873/anticanres.15351 |
| Popis: | BACKGROUND Head and neck cancer (HNC) is common worldwide. Given poor outcomes for patients with HNC, research into targeted therapies is needed. Ataxia telangiectasia mutated (ATM) is a DNA damage kinase which is activated by double-strand DNA breaks. We tested the effects of a novel ATM inhibitor on HNC cell lines and xenografts. MATERIALS AND METHODS p53-Binding protein 1 and phosphorylated ATM were localized in cultured cells by immunofluorescence microscopy. Protein expression was determined by western blot. Tumor xenografts were established by injecting HNC lines into immunocompromised mice. Tumor sections were characterized by immunohistochemistry. Apoptotic cells were determined by terminal transferase-mediated dUTP nick-end labeling assay. RESULTS ATM inhibition increased double-strand DNA breaks at replication foci in HNC cell lines. ATM inhibition affected cell-cycle regulatory protein expression, blocked cell-cycle progression at the G2/M phase and resulted in apoptosis. CONCLUSION ATM inhibition may be therapeutically useful in treating HNC. |
| Databáze: | OpenAIRE |
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