Alteration of the ß-catenin pathway in spiradenoma.

BACKGROUND: Although skin carcinogenesis has been widely investigated, only limited information is available for epidermal tumors, while even less is known about other skin structures. Alterations in the ß-catenin pathway have been reported in several epidermal tumors, while little is known about in adnexal tumors. This study was performed to assess alterations in the ß-catenin pathway associated with adnexal tumors, and to investigate the mechanisms underlying these alterations. METHODS: ß-Catenin expression in 48 adnexal tumors (trichoepithelioma, trichofolliculoma, pilomatricoma, syringoma, eccrine poroma, spiradenoma, sebaceous hyperplasia and nevus sebaceus) was assessed using immunohistochemistry. The tumors showing intense nuclear reactivity for ß-catenin were further evaluated by immunohistochemistry for ß-catenin degradation complex such as adenomatosis polyposis coli (APC), Axin and glycogen synthase kinase 3ß (GSK-3ß). RESULTS: Intense nuclear immunoreactivity for ß-catenin was observed in pilomatricoma and spiradenoma. Among 12 eccrine spiradenomas, APC was downregulated in 2 (16.7%) cases, and Axin and GSK-3ß were downregulated in 11 (91.7%) and 10 (83.3%) cases, respectively. CONCLUSIONS: This is the first reported analysis of the role of alterations in the ß-catenin pathway in spiradenoma. We suggest that downregulation of Axin and GSK-3ß in the ß-catenin pathway may be an important signaling alteration in the development of spiradenoma.

Epigallocatechin-3-gallate suppresses IGF-I-induced lipogenesis and cytokine expression in SZ95 sebocytes.

Acne vulgaris is the most common disease of the pilosebaceous unit. The pathogenesis of this inflammatory disease is complex, involving increased sebum production and perifollicular inflammation. To identify effective agents for factors that induce acne vulgaris, we explored the pharmacological potential of epigallocatechin-3-gallate (EGCG), which has been widely investigated as an anti-proliferative and anti-inflammatory agent. In this study, we demonstrated that topical application of EGCG to rabbit auricles reduced the size of the sebaceous glands. When applied to cultured human SZ95 sebocytes, EGCG strongly suppressed cell proliferation and lipogenesis. These actions of EGCG were reproduced in IGF-I-differentiated SZ95 sebocytes. To investigate the anti-inflammatory potential of EGCG, we evaluated pro-inflammatory cytokine synthesis in IGF-I-differentiated SZ95 sebocytes and found that expression of IL-1, IL-6, and IL-8 was decreased. These results provide early evidence that EGCG is an effective candidate for acne therapy whose mechanisms of action in IGF-I-differentiated SZ95 sebocytes include the inhibition of lipogenesis and inflammation.