Abstract 1553: Down-expression of ATM gene and protein associated with canine breast tumors.

Abstract

Abstract Background: Ataxia telangiectasia mutated (ATM) gene encodes a protein associated with DNA damage repair that plays an important role in the maintenance of genome integrity. ATM transcript and protein down-regulation have been reported in sporadic breast carcinomas and the absence of ATM protein expression was also significantly associated with distant metastasis in women, but the mechanisms involved in the ATM deregulation are not well established. Aim: Due to the fact that mammary tumor biological behavior is similar between canine and humans, we evaluate ATM gene and protein expression in canine breast cancer and compared with normal mammary gland from dogs. Patients and methods: Fresh samples of non-metastatic (n=23) and metastatic mammary carcinomas (n=11) and normal breasts (n=10) were evaluated for ATM gene expression by RT-qPCR and from the same animals, another sample of tumor was collected, formalin-fixed and paraffin-embedded to assess ATM protein expression by immunohistochemistry. Evaluation of ATM protein expression was performed by the distribution of positively-immunostained tumor cells in scores: 1 (<25% cells positive), 2 (26% to 50% cells positive) and 3 (>51% cells positive). Results: Down expression of ATM was detected in tumors samples (non-metastatic and metastatic mammary carcinomas) when compared to normal breast samples (P= 0,0414). Additionally, scores 1 and 2 of ATM protein expression were exclusively observed in metastatic tumors presenting score 1: 18% (2 out of 11), score 2: 55% (6 out to 11) and non metastatic tumors presenting the same score 1 and 2: 17% (4 out to 23) while all normal breast tissues showed score 3 (P=0,0087). Conclusions: Down expression of ATM transcript was confirmed by ATM protein expression. Low levels of ATM suggest an involvement of DNA damage repair transcript and protein in tumorigenesis process of canine mammary tumors, as in women, corroborating for the use of dogs as a natural comparative model to study mammary gland tumors in humans. Citation Format: Talita Mariana Morata Raposo, Renata C. Bueno, Márcio de Carvalho, Carlos E. Fonseca-Alves, Mirela Tinucci-Costa, Andrigo B. De Nardi, Silvia R. Rogatto, Renée Laufer-Amorim. Down-expression of ATM gene and protein associated with canine breast tumors. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1553. doi:10.1158/1538-7445.AM2013-1553