光线性角化病和鳞状细胞癌表皮生长因子受体与MAPK信号通路的研究  

Epidermal growth factor receptor and MAPK signaling pathways in actinic keratosis and cutaneous squamouscell carcinoma

作　　者：葛新红[1] 唐真真[2] 焦亚宁[1] 王乐[1] 杨晶[1] 董灵娣[1] 侯晶梅[2] 吴昊[2] 杨彪[2] 

机构地区：[1]宁夏医科大学总医院皮肤科,银川750004 [2]宁夏医科大学

出　　处：《中华皮肤科杂志》2015年第7期451-454,共4页Chinese Journal of Dermatology

基　　金：国家自然科学基金（81060181）;宁夏自然科学基金（NZ14121）

摘　　要：目的探讨磷酸化ERKl／2、JNK和p38MAPK与其上游因子表皮生长因子受体（EGFR）及下游转录因子Elk-1在光线性角化病（AK）和皮肤鳞状细胞癌（scc）中的表达。方法收集确诊为AK和高、中、低分化SCC患者各30例的病变组织，同时收集30例非癌患者正常皮肤组织作为正常对照组。采用免疫组化及Western印迹法分别检测p-EGFR、P—ERKI~、P—JNK、P—p38MAPK及p—Elk-1蛋白在AK和不同分化程度SCC中的表达情况。结果P—EGFR在SCC组中的表达高于AK组及正常对照组（P〈0．05），AK组与正常对照组表达差异无统计学意义；P—ERKl／2、P—JNK、P—p38MAPK及p-Elk-1在SCC的表达均高于AK组及正常对照组（P〈0．05），且在AK中的表达又均高于正常对照组（P〈0．05）。除p-EGFR和p-Elk-1在高分化和中分化SCC中的表达差异无统计学意义，p-ERKl／2、P—JNK、P—p38MAPK随着SCC分化程度的降低，其表达逐渐增高（P〈0．05）。相关性分析显示，在SCC中p-EGFR的表达与p-ERKI~、P—JNK、P—p38MAPK的表达强度呈正相关（r=0．843、0．819、0．902，均P〈0．01），且p-Elk-1的表达与p-ERKl／2、P—JNK、P—p38MAPK的表达强度亦呈正相关（r=0．874、0．843、0．893，均P〈0．01）；在AK中P—EGFR的表达仅与P—p38MAPK的表达强度呈正相关（r=0．707，P=0．022）。结论p-EGFR、P—ERKI、P—JNK、P—p38MAPK及P—Elk-1蛋白在皮肤SCC中的表达与其病理分级有关。磷酸化EGFR--ERKI／2、JNK、p38MAPK---Elk-1信号转导途径可能在AK和SCC的发生发展中起作用。Objective To measure the expressions of phosphorylated ERK1/2 （p-ERK1/2）, p-JNK, p-p38 mitogen-activated protein kinase （p-p38 MAPK）, their upstream epidermal growth factor receptor （EGFR） and downstream transcription factor Elk-1 in actinic keratosis （AK） and cutaneous squamous cell carcinoma （SCC）. Methods Skin specimens were resected from the lesions of patients with AK, well-, moderately- and poorly-differentiated SCC and from normal skin of 30 healthy human controls. The number of skin specimens of AK and SCC at different degrees of differentiation was uniformly 30, with the total number of lesional specimens being 120. Both immunohistochemistry and Western blot were performed to measure the expressions of p-EGFR, p-ERK1/2, p-JNK, p-p38MAPK and p-Elk-1 in these specimens. Statistical analysis was carried out by using one-way analysis of variance and Pearson correlation analysis. Results The immunohistochemical study showed that p-EGFR expression was significantly higher in SCC than in AK and normal skin specimens （both P 〈 0.05）, but no significant difference was observed between AK and normal skin specimens. The expressions of p-ERK1/2, p-JNK, p-p38MAPK and p-Elk-1 were all significantly higher in SCC than in AK and normal skin specimens （all P 〈 0.05 ）, and higher in AK than in normal skin specimens （all P 〈 0.05）. The expressions of p-ERK1/2, p-JNK and p-p38MAPK in SCC increased with the decrease in differentiation degree of SCC （all P 〈 0.05）, while there was no statistical difference in the expressions of p-EGFR or p-Elk-1 between well- and moderately-differentiated SCC specimens. Western blot results were similar to the immunohistochemical results. The expression intensity of p-EGFR was positively correlated with that of p-ERK1/2, p-JNK and p-p38MAPK respectively in SCC （r= 0.843, 0.819, 0.902, respectively, all P〈 0.01）, so was that of p-Elk-1 （r= 0.874, 0.843, 0.893, respectively, all P 〈 0.01 ）. The expression intensity of p-EGFR was only posit

关 键 词：肿瘤 鳞状细胞 角化病 光化性 受体 表皮生长因子 信号传导 MAP激酶信号系统 p38丝 裂原活化蛋白激酶类 

分 类 号：R758.1[医药卫生—皮肤病学与性病学] R739.5[医药卫生—临床医学]