b-Catenin, encoded by the ctnnb1 gene, plays a critical role in intercellular adhesion, and its altered expression has been implicated in tumor progression in humans and animals. The aims of this study were to examine the alterations in b-catenin expression in canine melanoma as well as the causes of these changes (eg, E-cadherin or exon 3 mutations) and to compare identified changes between skin and oral melanomas. Forty-two primary canine skin and oral melanoma tissue samples were used in the study. The expression levels of ctnnb1 and the levels of E-cadherin/b-catenin complex in the tissues were determined by semiquantitative RT-PCR and immunohistochemistry, respectively. The mutational status of b-catenin exon 3 was examined by DNA sequencing. RT-PCR revealed higher levels of ctnnb1 expression in oral melanoma tissues compared with normal melanocytes, irrespective of sex or histopathological appearance of the tissue (ie, amelanotic vs melanotic). Immunohistochemistry revealed simultaneous loss of membrane E-cadherin/b-catenin complex and cytoplasmic accumulation of both proteins in 37 cases (84%). Intranuclear b-catenin was also detected in all tissues with reduced membrane b-catenin expression. In mutational analyses, one amelanotic oral melanoma showed 13 single nucleotide polymorphisms (SNPs); however, after protein translation, all the SNPs were silent mutations. The present study demonstrates that dysregulation of E-cadherin/b-catenin complexes is involved in both types of canine melanotic tumors and that the disruption of E-cadherin/b-catenin complexes and increased b-catenin may induce tumor progression and malignancy.

Our previous study showed that anacardic acid (AA) suppressed ultraviolet (UV)-induced histone modification, matrix metalloproteinase (MMP)-13, MMP-9, cyclooxygenase-2 and tumor necrosis factor-alpha expressions in hairless mice skin. To determine the photoprotective and anti-inflammatory effects of AA in human skin, the buttock of young subjects (age 21-39 yr, n¼9) was irradiated with 2 minimal erythema dose (MED) of UV, and topically treated with 0.1% AA or its vehicle after UV irradiation. Topical treatment with AA did not only reduce UV-induced increases in erythema index as measured by Mexameter TM , but also prevented UV-induced increased expression of MMP-1 and interleukin-6. In addition, AA inhibited UV-induced expression of acetyl-H3 and g-H2AX, a DNA damage marker. Our data suggest that the topical application of AA, an inhibitor of p300 histone acetyltransferase, may prevent UV-induced untoward skin responses via epigenetic regulation, suggesting that epigenetic modifications may provide effective therapeutic measures for the prevention and treatment of photoaging.

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