Hormonal Carcinogenesis in Canine Mammary Cancer: Molecular Mechanisms of Estradiol Involved in Malignant Progression

SIMPLE SUMMARY: Canine mammary cancer corresponds to a tumor disease that frequently affects female dogs, especially those that are reproductively intact. This disease can decrease the survival and quality of life of affected animals; therefore, it is important to know the underlying mechanisms. Hormonal factors are very important for the development of this pathology. Estradiol, a hormone produced primarily in the ovaries actively participates in the process of mammary tumor formation, but the principal mechanisms behind this carcinogenic role remain incompletely understood. This review will discuss how estradiol would induce its pro-tumor effect on the mammary tissue, thus contributing to the understanding of the mechanisms involved in the development of this disease. ABSTRACT: Mammary cancer is a frequent neoplasia in female dogs, in which most important risk factors are hormonal. Sexual hormones as estradiol play an important role in mammary carcinogenesis, being able to induce carcinogenic initiation, promotion and progression. However, the molecular mechanisms involved are incompletely understood. Estradiol is synthesized mainly in the ovaries, nevertheless, high concentrations of estradiol and some of its hormonal precursors have also been described in malignant mammary tumor tissue. The mechanisms of action of estradiol include the classic genomic effects that modulate gene transcription, and non-genomic effects, which trigger quick effects after estradiol binds to its specific receptors. These responses modulate various intracellular signaling pathways, triggering post-translational modification of several proteins. This review will discuss the well-known underlying mechanisms associated with the action of estradiol in the malignant progression of canine mammary tumors.