Molecular abnormalities of cell cycle regulations in epidermal keratinocytes for the clinical applications

点击翻译按钮获取中文摘要

To elucidate molecular abnormalities of cell cycle regulations in epidermal keratinocytes for the clinical applications, we have investigated expression of cell cycle regulators of p14,p16,p21,p27, and SIRT1 in skin tumors, including squamous cell carcinoma (SCC), basal cell carcinoma (BCC), Bowen's disease (BD), actinic keratosis (AK), and seborrheic keratosis (SK). Protein products of p14,p16,p21 and p27 regulate cell cycle negatively in response to stress stimuli in vitro. SIRT1, a mammalian homolog of yeast Sir2 that increases longevity, is a deacetylase associated with cell cycle. 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. We have examined SIRT1 protein expression in 20 cases each of SCC, BCC, BD, AK, and SK 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 SIRTI 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.