Expression of acetylated histones H3 and H4 and histone deacetylase enzymes HDAC1, HDAC2 and HDAC6 in simple mammary carcinomas of female dogs.

Autor:	Senhorello ILS; Department of Veterinary Clinic and Surgery, Faculty of Agricultural and Veterinary Sciences, Universidade Estadual Paulista, Jaboticabal, SP, Brazil.; Department of Veterinarry Medicine, Universidade Vila Velha-UVV, Vila Velha, Espírito Santo, Brazil., Matiz ORS; Department of Veterinary Clinic and Surgery, Faculty of Agricultural and Veterinary Sciences, Universidade Estadual Paulista, Jaboticabal, SP, Brazil., Canavari IC; Department of Veterinary Clinic and Surgery, Faculty of Agricultural and Veterinary Sciences, Universidade Estadual Paulista, Jaboticabal, SP, Brazil., Hernandez GV; Department of Animal Health, Universidad Nacional de Colombia, Bogotá, Colombia., Anai LA; Autonomous Veterinarian, São Paulo, Brazil., Navarrete Ampuero RA; Autonomous Veterinarian, São Paulo, Brazil., Pazzini JM; Autonomous Veterinarian, São Paulo, Brazil., Prado CM; Department of Veterinary Medicine, Faculty of Animal Science and Food Engineering, Universidade de São Paulo-USP, Pirassununga, São Paulo, Brazil., Meirelles FV; Department of Veterinary Medicine, Faculty of Animal Science and Food Engineering, Universidade de São Paulo-USP, Pirassununga, São Paulo, Brazil., Vasconcelos RO; Department of Veterinary Clinic and Surgery, Faculty of Agricultural and Veterinary Sciences, Universidade Estadual Paulista, Jaboticabal, SP, Brazil., Tinucci-Costa EM; Department of Veterinary Clinic and Surgery, Faculty of Agricultural and Veterinary Sciences, Universidade Estadual Paulista, Jaboticabal, SP, Brazil.
Jazyk:	angličtina
Zdroj:	Frontiers in genetics [Front Genet] 2023 Nov 09; Vol. 14, pp. 1257932. Date of Electronic Publication: 2023 Nov 09 (Print Publication: 2023).
DOI:	10.3389/fgene.2023.1257932
Abstrakt:	Histone deacetylation is an important mechanism involved in human breast cancer tumorigenesis and recent veterinary oncology studies also demonstrate a similar relationship in some canine neoplasms. The use of HDAC inhibitors in vitro and in vivo has demonstrated antitumor action on several strains of human and animal cancers. The present study aims to correlate the expression of H3K9Ac, H4K12Ac, HDAC1, HDAC2 and HDAC6 in simple mammary carcinomas in dogs with clinicopathological parameters and overall survival time. To this end, 61 samples of simple breast carcinomas were analyzed by the immunohistochemistry technique with subsequent validation of the antibodies by the Western Blot technique. The expressions obtained via a semi-quantitative way were categorized by assigning scores and classified into high or low expressions according to the given score, except for HDAC6, when the marking percentage was considered and subdivided into high and low expressions using the median value. For statistical analysis, the chi-square test or Fisher exact test were used as univariate analysis and correspondence analysis as a multivariate test, in addition to the Kaplan-Meier survival analysis. In the studied samples, the highest frequencies were determined for the high expression proteins H4K12Ac (88.5%), HDAC2 (65.6%) and HDAC6 (56.7%) and the low expression proteins H3K9Ac (73.8%) and HDAC1 (54.1%). An association between the low expression of HDAC1 and the presence of lymph node metastasis ( p = 0.035) was indicated by univariate analysis while the high expression of HDAC1 was associated with favorable prognostic factors, such as the absence of lymph node metastasis and low mitotic index by multivariate analysis. Also, by multivariate analysis, the low expression of HDAC6 was correlated with the low expression of Ki67, smaller tumors, and better prognosis factors as well. Protein expression was not correlated with patients' overall survival time ( p > 0.05). The high expressions of HDAC2 and HDAC6 in mammary carcinomas in female dogs may be useful information for research involving therapeutic targets with iHDACs since their inhibition favors hyperacetylation and transcription of tumor suppressor genes. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision (Copyright © 2023 Senhorello, Matiz, Canavari, Hernandez, Anai, Navarrete Ampuero, Pazzini, Prado, Meirelles, Vasconcelos and Tinucci-Costa.)
Databáze:	MEDLINE
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