Dysregulation of the Wnt/beta-catenin signaling pathway in canine cutaneous melanotic tumor.

Abstract

The Wnt/beta-catenin signal transduction pathway is important in many developmental processes and during tumorigenesis. beta-Catenin acts as a signal transducer. To investigate whether the Wnt/beta-catenin signal transduction pathway is involved in canine cutaneous melanomagenesis, 18 formalin-fixed paraffin-embedded canine cutaneous melanotic tumor tissues were examined. For cloning and sequencing of the full-length canine ctnnb1 gene encoding beta-catenin, conserved sequences of the human and mouse ctnnb1 gene were used to design the primers. For analysis of expression and translocation of beta-catenin in canine cutaneous melanotic tumors, semiquantitative reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry were performed. The canine ctnnb1 sequence showed a high degree of similarity to those of human and mouse. Semiquantitative RT-PCR showed a substantial increase in expression of ctnnb1 mRNA in canine cutaneous melanotic tumors compared to normal canine melanocytes, regardless of whether the tumor was benign or malignant. Immunohistochemistry revealed cytoplasmic accumulation of beta-catenin in melanotic tumors. In melanoma tissues, nuclear translocation of beta-catenin was also observed. The present study demonstrated that abnormal intracellular accumulation and substantially increased expression of beta-catenin are involved in canine cutaneous melanotic tumor.