Characterization of WWOX expression and function in canine mast cell tumors and malignant mast cell lines
| Autor: | Justin T. Breitbach, Hanna Cook, Darian S. Louke, Christopher Premanandan, Joelle M. Fenger, Eric M. Green, Rebecca Makii, Ryan N. Jennings |
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| Rok vydání: | 2020 |
| Předmět: |
WWOX
Skin Neoplasms Tumor suppressor gene Canine Mastocytoma Biology DNA damage response 03 medical and health sciences 0302 clinical medicine Dogs Cell Line Tumor medicine Animals Mast Cells 030304 developmental biology 0303 health sciences Tissue microarray lcsh:Veterinary medicine General Veterinary Tumor Suppressor Proteins General Medicine Mastocytoma Mast cell Gene Expression Regulation Neoplastic Haematopoiesis medicine.anatomical_structure WW Domain-Containing Oxidoreductase Cell culture 030220 oncology & carcinogenesis Cancer research Immunohistochemistry lcsh:SF600-1100 Canine mast cell tumors Research Article |
| Zdroj: | BMC Veterinary Research BMC Veterinary Research, Vol 16, Iss 1, Pp 1-13 (2020) |
| ISSN: | 1746-6148 |
| Popis: | Background The WW domain-containing oxidoreductase (WWOX) tumor suppressor gene is frequently lost in a variety of solid and hematopoietic malignancies in humans. Dysregulation of WWOX has been implicated as playing a key role in tumor cell survival, DNA damage repair, and genomic stability. The purpose of this study was to characterize WWOX expression in spontaneous canine mast cell tumors (MCTs) and malignant cell lines and investigate the potential contribution of WWOX loss on malignant mast cell behavior. Methods/results WWOX expression is decreased in primary canine MCTs and malignant mast cell lines compared to normal canine bone marrow-cultured mast cells. In transformed canine mastocytoma cell lines, overexpression of WWOX or WWOX knockdown had no effect on mast cell viability. Inhibition of WWOX enhanced clonogenic survival following treatment with ionizing radiation in the C2 mast cell line. Lastly, immunohistochemistry for WWOX was performed using a canine MCT tissue microarray, demonstrating that WWOX staining intensity and percent of cells staining for WWOX is decreased in high-grade MCTs compared to low-grade MCTs. Conclusions These data suggest that WWOX expression is attenuated or lost in primary canine MCTs and malignant mast cell lines. Given the observed increase in clonogenic survival in WWOX-deficient C2 mast cells treated with ionizing radiation, further investigation of WWOX and its role in mediating the DNA damage response in malignant mast cells is warranted. |
| Databáze: | OpenAIRE |
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