Molecular Carcinogenesis of Canine Mammary Tumors

Abstract

Studies focusing on the molecular basis of canine mammary tumors (CMT) have long been hampered by limited numbers of molecular tools specific to the canine species. The lack of molecular information for CMT has impeded the identification of clinically relevant tumor markers beyond histopathology and the introduction of new therapeutic concepts. Additionally, the potential use for the dog as a model for human breast cancer is debatable until questions are answered regarding cellular origin, mechanisms, and cellular pathways. During the past years, increasing numbers of canine molecular tools have been developed on the genomic, RNA, and protein levels, and an increasing number of studies have shed light on specific aspects of canine carcinogenesis, particularly of the mammary gland. This review summarizes current knowledge on the molecular carcinogenesis of CMT, including the role of specific oncogenes, tumor suppressors, regulators of apoptosis and DNA repair, proliferation indices, adhesion molecules, circulating tumor cells, and mediators of angiogenesis in CMT progression and clinical behavior. Whereas the data available are far from complete, knowledge of molecular pathways has a significant potential to complement and refine the current diagnostic and therapeutic approach to this tumor type. Furthermore, current data show that significant similarities and differences exist between canine and human mammary tumors at the molecular level. Clearly, this is only the beginning of an understanding of the molecular mechanisms of CMT and their application in clinical patient management.

Celecoxib exerts antitumor effects in canine mammary tumor cells via COX-2-independent mechanisms

“…accordingly, several studies have explored molecular markers to diagnose or treat malignant canine mammary tumors. Among these, COX-2 has received significant attention as a diagnostic and therapeutic target (11)(12)(13). furthermore, previous reports suggested that canine mammary tumors could be a suitable model for studying human breast cancer (14).…”

Histologic Evidence of the "Sick Lobe" Carcinogenesis Theory and the Frequency of Intraepithelial Lesions in the Mammary Glands of Female Canines with no Clinical Signs of Neoplasia

“…Factors including hormone levels, genetic predisposition, diet, environmental factors and hormone therapy have been suspected as risk factors for the development of canine mammary gland tumors, but a definitive cause(s) has not been definitively demonstrated [4,8].…”

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“…In female canines, mammary tumors are considered one of the most important cancers due to their high prevalence [4][5][6] and represent nearly 20% of all tumors in this species [7]. A new classification for this type of neoplasia in female canines was recently released and is very similar to that established for human females, with one important difference being the existence of complex tumors (with epithelial and myoepithelial components) in dogs.…”