CAJ | 학술논문

目的观察表皮生长因子受体相关蛋白(ERRP)的表达以及细胞增殖在胃癌分化和发展中的作用.方法观察47例患者胃癌的手术标本中ERRP的表达和定位,并将其与良性胃黏膜比较,确定他们与细胞增殖和分化的关系.检测3种不同的胃癌细胞株中ERRP的表达,并用表皮生长因子(EGF)诱导EGFR磷酸化激活MKN-28胃癌细胞,检测ERRP对此效应的作用.结果与良性胃黏膜(66％标本阳性)比较,胃癌(33％标本阳性)中ERRP的表达显著降低.正常胃黏膜的ERRP染色评分是2.9(0.3),高分化、中度分化和低分化癌的评分分别是2.6(0.6)、0.9(0.6)和1.0(0.5),ERRP表达的降低与恶性程度的组织学分级呈负相关(P＜0.05).ERRP阴性癌细胞[35.3(1.1)％；P＜0.01]中增殖程度是ERRP附性癌细胞[9.4(0.6)％]的3.5倍,ERRP在癌细胞中的表达与细胞增殖也呈负相关.与源于非转移性癌的细胞AGC比较,源于转移性胃癌细胞MKN-28和NCI-N87中ERRP的表达量分别是其的1.7倍和2倍.外源性的ERRP蛋白明显抑制了EGF诱导的胃癌细胞MKN-28中EGFR的磷酸化,抑制程度为45倍.结论 ERRP的下调可能在胃癌分化和发展中起重要的作用.ERRP对肿瘤细胞增殖具有负调控作用,其抑制作用可能部分是通过减弱EGFR的活化来实现的.
목적 관찰표피생장인자수체상관단백(ERRP)적표체이급세포증식재위암분화화발전중적작용.방법 관찰47례환자위암적수술표본중ERRP적표체화정위,병장기여량성위점막비교,학정타문여세포증식화분화적관계.검측3충불동적위암세포주중ERRP적표체,병용표피생장인자(EGF)유도EGFR린산화격활MKN-28위암세포,검측ERRP대차효응적작용.결과 여량성위점막(66％표본양성)비교,위암(33％표본양성)중ERRP적표체현저강저.정상위점막적ERRP염색평분시2.9(0.3),고분화、중도분화화저분화암적평분분별시2.6(0.6)、0.9(0.6)화1.0(0.5),ERRP표체적강저여악성정도적조직학분급정부상관(P＜0.05).ERRP음성암세포[35.3(1.1)％；P＜0.01]중증식정도시ERRP부성암세포[9.4(0.6)％]적3.5배,ERRP재암세포중적표체여세포증식야정부상관.여원우비전이성암적세포AGC비교,원우전이성위암세포MKN-28화NCI-N87중ERRP적표체량분별시기적1.7배화2배.외원성적ERRP단백명현억제료EGF유도적위암세포MKN-28중EGFR적린산화,억제정도위45배.결론 ERRP적하조가능재위암분화화발전중기중요적작용.ERRP대종류세포증식구유부조공작용,기억제작용가능부분시통과감약EGFR적활화래실현적.
Objective To investigate the role of Epidermal growth factor receptor related protein in gastric cancer differentiation and progression.Methods Examined epidermal growth factor receptor associated protein(ERRP) expression and localisation in surgical specimens of gastric cancers from 47 patients versus non-malignant gastric mucosa and determined their relationship to cell proliferation and differentiation.Examined expression of ERRP by western blotting in three different gastric cancer cell lines.To further determine the functional properties of ERRP,we examined the effect of ERRP on epidermal growth factor (EGF) induced epidermal growth factor recepto (EGFR) phosphorylation essential for its activation in MKN-28 gastric cancer cells.Results ERRP expression was dramatically reduced in gastric cancers (34％ of all specimens positive) compared with non-malignant gastric mucosa (66％ of specimens positive).Cell proliferation was also significantly (3.5 fold) lower in ERRP positive cancer cells (9.4(0.6) ％ ) than in ERRP negative cancer cells (35.3 ( 1.1 ) ％ ; P ＜ 0.01 ).Expression of ERRP in cancer cells inversely correlated with cell proliferation and grade of malignancy ( P ＜ 0.05 ).ERRP expression levcls were markedly decreased in the metastases derived cells MKN-28 (1.7-fold) and NCI-N87 (2 fold) compared with the non-metastatic gastric cancer cell line (AGS) which is poorly differentiated.Exogenous ERRP protein markedly inhibited EGF induced EGFR phosphorylation (45 fold) in gastric cancer cells providing a novel molecular mechanism of its action.Conclusion ERRP could play an important role in gastric cancer differentiation and progression.ERRP is a negative regulator of tumour cell proliferation and may exert its inhibitory effect,in part,by attenuating EGFR activation.