Hida Yasutoshi, Kubo Yoshiaki, Murao Kazutoshi, Arase Seiji
Department of Dermatology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
Arch Dermatol Res. 2007 May;299(2):103-6. doi: 10.1007/s00403-006-0725-6. Epub 2006 Dec 20.
The class III histone deacetylase (HDAC), SIRT1, is a mammalian homologue of the Saccharomyces cerevisiae chromatin-silencing factor Sir2 that regulates longevity. SIRT1 regulates cell survival via deacetylation of p53 and forkhead transcription factors, and overexpression of SIRT1 is reported to be essential for cell growth and survival in some kinds of cancer. To elucidate the role of SIRT1 in human skin carcinogenesis, we have examined SIRT1 protein expression in 20 cases each of squamous cell carcinoma (SCC), basal cell carcinoma (BCC), Bowen's disease (BD), and actinic keratosis (AK) by immunohistochemical analysis. Overexpression of SIRT1 is frequently observed in all kinds of non-melanoma skin cancers included in this study. In particular, strong expression was observed in all cases of BD. In addition, no obvious difference between AK and SCC was observed in the expression of SIRT1, suggesting that overexpression of SIRT1 may have some relevance to the early stage of skin carcinogenesis. We suppose that SIRT1 could be one of the critical targets for future therapy with the aim of inhibiting cell proliferation and promoting apoptosis in non-melanoma skin cancers.
Ⅲ类组蛋白去乙酰化酶（HDAC）SIRT1是酿酒酵母染色质沉默因子Sir2的哺乳动物同源物，可调节寿命。SIRT1通过使p53和叉头转录因子去乙酰化来调节细胞存活，据报道，SIRT1的过表达对某些类型癌症中的细胞生长和存活至关重要。为了阐明SIRT1在人类皮肤癌发生中的作用，我们通过免疫组织化学分析检测了20例鳞状细胞癌（SCC）、基底细胞癌（BCC）、鲍温病（BD）和光化性角化病（AK）中SIRT1蛋白的表达。在本研究纳入的各类非黑素瘤皮肤癌中，经常观察到SIRT1的过表达。特别是，在所有BD病例中均观察到强表达。此外，在AK和SCC的SIRT1表达中未观察到明显差异，这表明SIRT1的过表达可能与皮肤癌发生的早期阶段有一定关联。我们推测，SIRT1可能是未来治疗非黑素瘤皮肤癌的关键靶点之一，其目的是抑制细胞增殖并促进细胞凋亡。
