Department of Bio-medical Sciences, Section of Physiology, University of Catania, Viale A. Doria 6, 95125 Catania, Italy.
Acta Histochem. 2013 Oct;115(8):795-802. doi: 10.1016/j.acthis.2013.03.003. Epub 2013 Apr 17.
Melanoma, a cancer notorious for its high potential to metastasize, arises from melanocytes, cells dedicated to melanin production and located in the basal layer of the epidermis. Raf-1 kinase inhibitor protein (RKIP) is an inhibitory molecule that down-regulates the effects of the Ras/Raf/MEK/ERK signaling pathway. The aim of this study was to examine the expression of RKIP and pRKIP in melanomas at different stages. We evaluated the RKIP and pRKIP protein by immunohistochemistry in control skin, pigmented nevi and melanomas, and through Western blotting in human normal melanocytes and in four different melanoma-derived cell lines (WM35, A375, M14, and A2058). Our results demonstrated a correlation between the expression of RKIP and pRKIP, and metastatic ability in melanoma cells. This raises the possibility to analyze both RKIP and pRKIP in all melanomas. Down-regulation of both RKIP and pRKIP expression could represent a useful marker of metastatic melanoma. On the contrary for non-metastatic melanoma, especially in Clark I and II, low RKIP and high pRKIP expression could be indicative. In conclusion, the observed negative correlation of the RKIP and pRKIP expression in metastatic melanomas indicates that expression of these proteins may become a prognostic marker for the progression of human cutaneous melanoma. We propose that the investigation of both RKIP and pRKIP may provide a useful tool indicative for metastatic or non-metastatic melanoma in different Clark's level melanomas. Further studies are required to verify the molecular background of the observed RKIP and pRKIP variations.
黑色素瘤是一种恶性肿瘤，具有高度转移的潜力，它起源于黑色素细胞，这些细胞专门负责黑色素的生成，位于表皮的基底层。Raf-1 激酶抑制剂蛋白（RKIP）是一种抑制分子，可下调 Ras/Raf/MEK/ERK 信号通路的作用。本研究旨在研究不同阶段黑色素瘤中 RKIP 和 pRKIP 的表达。我们通过免疫组织化学法在正常皮肤、色素痣和黑色素瘤中评估 RKIP 和 pRKIP 蛋白，并通过 Western blot 在人正常黑素细胞和四个不同的黑色素瘤衍生细胞系（WM35、A375、M14 和 A2058）中评估 RKIP 和 pRKIP 蛋白。我们的结果表明 RKIP 和 pRKIP 的表达与黑色素瘤细胞的转移能力之间存在相关性。这使得分析所有黑色素瘤中的 RKIP 和 pRKIP 成为可能。RKIP 和 pRKIP 表达的下调可能代表转移性黑色素瘤的一个有用标记。相反，对于非转移性黑色素瘤，特别是在 Clark I 和 II 期，低 RKIP 和高 pRKIP 表达可能是指示性的。总之，观察到转移性黑色素瘤中 RKIP 和 pRKIP 表达的负相关表明这些蛋白的表达可能成为人类皮肤黑色素瘤进展的预后标志物。我们提出，对 RKIP 和 pRKIP 的研究可能为不同 Clark 级别的黑色素瘤中的转移性或非转移性黑色素瘤提供一个有用的指示性工具。需要进一步的研究来验证观察到的 RKIP 和 pRKIP 变化的分子背景。
