Downregulation of ATM Gene and Protein Expression in Canine Mammary Tumors.
The ataxia telangiectasia mutated (ATM) gene encodes a protein associated with DNA damage repair and maintenance of genomic integrity. In women, ATM transcript and protein downregulation have been reported in sporadic breast carcinomas, and the absence of ATM protein expression has been associated with poor prognosis. The aim of this study was to evaluate ATM gene and protein expression in canine mammary tumors and their association with clinical outcome. ATM gene and protein expression was evaluated by reverse transcription-quantitative polymerase chain reaction and immunohistochemistry, respectively, in normal mammary gland samples (n = 10), benign mammary tumors (n = 11), nonmetastatic mammary carcinomas (n = 19), and metastatic mammary carcinomas (n = 11). Lower ATM transcript levels were detected in benign mammary tumors and carcinomas compared with normal mammary glands (P = .011). Similarly, lower ATM protein expression was observed in benign tumors (P = .0003), nonmetastatic mammary carcinomas (P < .0001), and the primary sites of metastatic carcinomas (P < .0001) compared with normal mammary glands. No significant differences in ATM gene or protein levels were detected among benign tumors and nonmetastatic and metastatic mammary carcinomas (P > .05). The levels of ATM gene or protein expression were not significantly associated with clinical and pathological features or with survival. Similar to human breast cancer, the data in this study suggest that ATM gene and protein downregulation is involved in canine mammary gland tumorigenesis.
Department of Veterinary Clinic and Surgery, UNESP, Jaboticabal, São Paulo, Brazil.
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Raposo-Ferreira
Department of Urology, Faculty of Medicine, UNESP, Botucatu, São Paulo, Brazil.
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Bueno
Department of Veterinary Clinic and Surgery, UNESP, Jaboticabal, São Paulo, Brazil.
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Terra
Department of Veterinary Clinic and Surgery, UNESP, Jaboticabal, São Paulo, Brazil.
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Avante
Department of Veterinary Clinic and Surgery, UNESP, Jaboticabal, São Paulo, Brazil.
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Tinucci-Costa
Department of Veterinary Clinic, UNESP, Botucatu, São Paulo, Brazil.
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Carvalho
Department of General Pathology, Institute of Biological Sciences, Federal University of Minas Gerais (UFMG), Belo Horizonte, Brazil.
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Cassali
Department of Urology, Faculty of Medicine, UNESP, Botucatu, São Paulo, Brazil.
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Linde
Department of Urology, Faculty of Medicine, UNESP, Botucatu, São Paulo, Brazil Neogene Laboratory, CIPE, A.C. Camargo Cancer Center, São Paulo, Brazil.
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0000-0003-4637-5687
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Rogatto
Department of Veterinary Clinic, UNESP, Botucatu, São Paulo, Brazil renee@fmvz.unesp.br.
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Laufer-Amorim
D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins / Q000235:genetics / Q000378:metabolism*; D016022:Case-Control Studies; D004283:Dog Diseases / Q000378:metabolism*; D004285:Dogs; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D008321:Mammary Glands, Animal / Q000378:metabolism; D015674:Mammary Neoplasms, Animal / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000662:veterinary
D064007:Ataxia Telangiectasia Mutated Proteins
ataxia telangiectasia mutated (ATM); breast cancer; canine mammary tumor; comparative oncology; metastasis; protein expression