Wnt/β-Catenin and Hippo Pathway Deregulation in Mammary Tumors of Humans, Dogs, and Cats

Mammary cancer is a common neoplasm in women, dogs, and cats that still represents a therapeutic challenge. Wnt/beta-catenin and Hippo pathways are involved in tumor progression, cell differentiation, and metastasis. The aim of this study was to evaluate mRNA and protein expression of molecules involved in these pathways in human (HBC), canine (CMT), and feline mammary tumors (FMT). Real-time quantitative polymerase chain reaction (qPCR) for beta-catenin,CCND1,YAP,TAZ,CTGF, andANKRD1, western blotting for YAP, TAZ, and beta-catenin, and immunohistochemistry for estrogen receptor (ER), progesterone receptor (PR), ERBB2, beta-catenin, and YAP/TAZ were performed on mammary tumor tissues. The protein expression of active beta-catenin was higher in tumors than in healthy tissues in all 3 species. The mRNA expression of the downstream geneCCND1was increased in HBC ER(+)and CMTs compared to healthy tissues. Membranous and cytoplasmic protein expression of beta-catenin were strongly negatively correlated in all 3 species. Tumors showed an increased protein expression of YAP/TAZ when compared to healthy tissues. Notably, YAP/TAZ expression was higher in triple negative breast cancers when compared to HBC ER(+)and in FMTs when compared to CMTs. The mRNA expression of beta-catenin,YAP,TAZ,CTGF, andANKRD1was not different between tumors and healthy mammary gland in the 3 species. This study demonstrates deregulation of Wnt/beta-catenin and Hippo pathways in mammary tumors, which was more evident at the protein rather than the mRNA level. Wnt/beta-catenin and Hippo pathways seem to be involved in mammary carcinogenesis and therefore represent interesting therapeutic targets that should be further investigated.