Department of Veterinary Pathology, College of Veterinary Medicine, reie Universität Berlin, Robert von Ostertag Str 15, D-14163 Berlin, Germany.
Vet Pathol. 2011 Jan;48(1):98-116. doi: 10.1177/0300985810390826. Epub 2010 Dec 13.
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.
长期以来，由于缺乏针对犬种的特定分子工具，专注于犬乳腺肿瘤（CMT）分子基础的研究一直受到限制。CMT 的分子信息缺乏，阻碍了除组织病理学以外的临床相关肿瘤标志物的识别和新治疗概念的引入。此外，在回答有关细胞起源、机制和细胞途径的问题之前，犬作为人类乳腺癌模型的潜在用途是值得商榷的。在过去的几年中，在基因组、RNA 和蛋白质水平上已经开发出越来越多的犬科分子工具，并且越来越多的研究揭示了犬类致癌作用的具体方面，特别是乳腺。这篇综述总结了目前关于 CMT 分子发生的知识，包括特定癌基因、肿瘤抑制基因、细胞凋亡和 DNA 修复调节剂、增殖指数、粘附分子、循环肿瘤细胞和血管生成介质在 CMT 进展和临床行为中的作用。虽然现有数据远非完整，但对分子途径的了解具有显著的潜力来补充和完善目前对这种肿瘤类型的诊断和治疗方法。此外，目前的数据表明，犬科和人类乳腺肿瘤在分子水平上存在显著的相似性和差异。显然，这只是了解 CMT 分子机制及其在临床患者管理中的应用的开始。
