The role of tumor suppressor genes in the pathogenesis of canine
melanoma is incompletely understood. The genes encoding the
tumor suppressors p53, Rb, p21 (waf-1), p16 (ink-4a), and PTEN have been postulated to contribute to the pathogenesis of
melanoma in humans and experimental animal models. To assess whether inactivation of these genes similarly contributes to the origin and progression of canine
melanoma, we examined their expression in seven distinct canine
melanoma cell lines and in 31 retrospective samples (representing 29 dogs) of spontaneous canine
melanoma. Various patterns suggestive of loss of
tumor suppressor function emerged in these cell lines. The most frequently observed abnormality was loss or significant reduction of p16 expression in six of seven cell lines and in 21 of 26
tumor samples. Loss or significant reduction of PTEN expression was seen in four of seven cell lines and in 13 of 27
tumor samples. Although p53 was detectable in all the cell lines and in 24 of 30
tumors, exclusion of p53 from the nuclear compartment was observed in each of the cell lines and in 18 of 25
tumor samples. These results indicate that loss of function of these
tumor suppressor proteins is a common occurrence that may contribute to the origin of canine
melanoma. In our sample population, abnormalities in the expression or localization of one or more
tumor suppressor proteins occurred with similar frequency in malignant and benign
tumors; thus, additional work is necessary to determine how these
proteins may impact
disease progression and response to
therapy.