Clinical significance of the expression of c-Ski and SnoN, possible mediators in TGF-β resistance, in primary cutaneous melanoma
Clinical significance of the expression of c-Ski and SnoN, possible mediators in TGF-β resistance, in primary cutaneous melanoma
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DOI：
10.1016/j.jdermsci.2008.07.010
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发表时间：
2009-01-01
影响因子：
4.6
通讯作者：
Brochez, Lieve
中科院分区：
文献类型：
--
作者：
Boone, Barbara;Haspeslagh, Marc;Brochez, Lieve
背景：失去对转化生长因子-β生长的控制被认为是包括黑色素瘤在内的几种人类肿瘤的特征。癌细胞对转化生长因子-β的抗药性与转化生长因子-β途径中涉及的蛋白质突变有关。在黑色素瘤中还没有观察到这样的突变。C-Ski和SnoN是结构上和功能上高度同源的两种蛋白，被认为是转化生长因子-β信号通路中的负调控因子。C-Ski和SnoN的表达水平和亚细胞定位与几种人类恶性肿瘤的临床病理参数和转归进展相关。目的：探讨c-Ski和SnoN在皮肤原发性黑色素瘤中的表达及其临床意义。方法：采用免疫组织化学方法检测120例皮肤原发黑色素瘤中c-Ski和SnoN的表达。分析c-Ski和SnoN染色模式与临床病理参数的关系。结果：c-Ski核表达与肿瘤增厚和溃烂显著相关。结论：c-Ski和SnoN作为转化生长因子-β抵抗的介导物，可能与黑色素瘤的生长和发展有关。(C)2008年日本皮肤病研究学会。爱思唯尔爱尔兰有限公司出版。版权所有。
Background: Loss of TGF-beta growth control is Considered as a hallmark of several human neoplasms including melanoma. Resistance of cancer cells to TGF-beta has been linked to mutations in proteins involved in the TGF-beta pathway. In melanoma such mutations have not been observed. C-Ski and SnoN, two structurally and functionally highly homologous proteins, are known as negative regulators in the TGF-beta signaling pathway. C-Ski and SnoN expression levels and subcellular localization have been associated with clinicopathological parameters and turnout Progression in several human malignancies. In melanoma cell lines, high c-Ski and SnoN expression levels have been described.Objective: The objective of this study was to evaluate the clinical value of c-Ski and SnoN expression in primary Cutaneous melanoma.Methods: We evaluated c-Ski and SnoN expression by immunohistochemical staining in 120 primary melanomas. Possible associations between c-Ski and SnoN staining patterns and clinicopathological parameters were analyzed.Results: Nuclear c-Ski expression was significantly associated with thicker and ulcerated tumours. The percentage of SnoN positivity was higher in ulcerated tumours and in the sentinel node positive group.Conclusion: These results suggest that c-Ski and SnoN, mediators in TGF-beta resistance, might be implicated in melanoma growth and progression. (c) 2008 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.