Mark Elisabeth Björntorp, Jonsson Marianne, Asp Julia, Wennberg Ann-Marie, Mölne Lena, Lindahl Anders
Department of Dermatology, Sahlgrenska University Hospital, Göteborg University, 413 45, Göteborg, Sweden.
Arch Dermatol Res. 2006 Apr;297(10):459-67. doi: 10.1007/s00403-006-0649-1. Epub 2006 Mar 22.
It has been suggested that the up-regulation of the tumour suppressor p16 gene and induction of senescence protect the phenotype of psoriatic involved skin from malignant transformation. On the other hand, Id1, which is inversely correlated with p16 has been shown to be up-regulated in psoriatic involved skin. To test the hypothesis that there may be an altered regulation of p16 in psoriatic involved skin, we have measured genes involved in the Igf-1 receptor signalling through the Ras/MAPK cascade. Igf-1R, IGFBP3, hRas, Ets2, JunB, Egr-1, Id1, MIDA1 and p16 gene expressions were measured using quantitative real-time PCR in total RNA isolated from punch biopsies from psoriatic involved (n = 9) and uninvolved skin (n = 9) and from cutaneous squamous cell cancer (SCC) involved (n = 8) and uninvolved skin (n = 8). The IGFBP3, hRas, JunB, Egr-1, Id1 and MIDA1 genes were up-regulated in psoriatic involved skin compared with uninvolved skin. The p16, JunB and MIDA1 genes were up-regulated in SCC involved skin compared with uninvolved skin. Our results indicate that there may be a balance between the proliferation and induction of senescence in psoriasis. This balance may vary and the psoriatic involved skin represented in this study appears to be in a proliferative state rather than senescence. Furthermore, we suggest that the noted up-regulation of JunB, which has been shown to up-regulate p16, in combination with the previously reported elevation of p16 expression in psoriatic involved skin, may indicate activation of a pathway by which JunB may protect the psoriatic plaque by inducing p16 in an event of malignant stress.
有人提出，肿瘤抑制因子p16基因的上调和衰老的诱导可保护银屑病受累皮肤的表型免于恶性转化。另一方面，与p16呈负相关的Id1在银屑病受累皮肤中已被证明上调。为了检验银屑病受累皮肤中p16的调节可能发生改变这一假设，我们测量了通过Ras/MAPK级联参与胰岛素样生长因子-1（Igf-1）受体信号传导的基因。使用定量实时PCR测量从银屑病受累皮肤（n = 9）和未受累皮肤（n = 9）以及皮肤鳞状细胞癌（SCC）受累皮肤（n = 8）和未受累皮肤（n = 8）的打孔活检中分离的总RNA中的Igf-1R、IGFBP3、hRas、Ets2、JunB、Egr-1、Id1、MIDA1和p16基因表达。与未受累皮肤相比，IGFBP3、hRas、JunB、Egr-1、Id1和MIDA1基因在银屑病受累皮肤中上调。与未受累皮肤相比，p16、JunB和MIDA1基因在SCC受累皮肤中上调。我们的结果表明，银屑病中增殖和衰老诱导之间可能存在平衡。这种平衡可能会有所不同，本研究中所代表的银屑病受累皮肤似乎处于增殖状态而非衰老状态。此外，我们认为，已证明可上调p16的JunB的上调，与先前报道的银屑病受累皮肤中p16表达升高相结合，可能表明存在一条途径被激活，在恶性应激情况下，JunB可能通过诱导p16来保护银屑病斑块。
