DNA Methylation Status of the Estrogen Receptor α Gene in Canine Mammary Tumors
| Autor: | Thierry Grima de Cristo, Mariana Busato Toledo, Giseli Klassen, Renato Silva de Sousa, Andressa Chequin, Yara de Oliveira Brandão, Edneia A.S. Ramos |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
040301 veterinary sciences Estrogen receptor Mammary Neoplasms Animal Biology Benign tumor 0403 veterinary science 03 medical and health sciences Dogs Biomarkers Tumor medicine Animals Epigenetics Promoter Regions Genetic General Veterinary Estrogen Receptor alpha Cancer 04 agricultural and veterinary sciences Methylation DNA Methylation Prognosis medicine.disease 030104 developmental biology CpG site DNA methylation Cancer research CpG Islands Female Estrogen receptor alpha |
| Zdroj: | Veterinary Pathology. 55:510-516 |
| ISSN: | 1544-2217 0300-9858 |
| DOI: | 10.1177/0300985818763711 |
| Popis: | Estrogen receptor α (ERα) has an important role in mammary carcinogenesis, prognosis, and treatment. In human and canine mammary cancer, the most aggressive tumors show loss of ERα expression, which in human breast cancer has been attributed to methylation of the cytosine followed by guanine (CpG) island within the estrogen receptor α gene ( ESR1) promoter. This study aimed to investigate the role of ESR1 CpG island (CGI) methylation in ERα expression in canine mammary tumors. Twenty-one canine mammary samples were sorted into three groups: malignant tumor (n = 9), benign tumor (n = 8), and normal gland (n = 4). Immunohistochemical analysis and reverse-transcription quantitative real-time PCR were performed to assess ERα expression and ESR1 mRNA levels. The methylation status was determined using sodium-bisulfite-treated DNA sequencing. All normal mammary glands and benign tumors showed high ERα expression (score range, 5–8). Six of the nine malignant tumors did not show ERα expression (score 0), two had score 2, and one had score 4. Lower ERα ( P < .005) and ESR1 mRNA levels ( P < .005) were found in malignant mammary tumors than in the other two groups. Canine ESR1 has an intragenic and non-promoter-associated CGI, different from humans. No significant variation in methylation percentage was observed among the groups, suggesting that ESR1 is not regulated by DNA methylation, unlike that in humans. This difference should be considered in further research using ERα as a biomarker for mammary tumors in canine studies on ERα-targeting therapy. |
| Databáze: | OpenAIRE |
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