PGRN调控EGFR在乳腺癌发生发展中的作用及其机制研究  

Expression of PGRN in breast cancer and its relation with EGFR

作　　者：王攀 林庆晨 王毅超 顾华敏 WANG Pan;LIN Qingchen;WANG Yichao;GU Huamin(Department of Clinical Laboratory,Taizhou Central Hospital(Affiliated Hospital of Taizhou College),Taizhou 318000,China)

机构地区：[1]台州市中心医院(台州学院附属医院)医学检验科,318000 [2]台州市中心医院(台州学院附属医院)病理科,318000

出　　处：《浙江医学》2024年第23期2475-2479,2485,I0004,共7页Zhejiang Medical Journal

基　　金：浙江省基础公益研究计划项目(LGF22H200007)。

摘　　要：目的探讨颗粒蛋白酶前体(PGRN)在乳腺癌中的表达,分析PGRN与表皮生长因子受体(EGFR)的相关性,了解PGRN调控EGFR在乳腺癌发生和发展中的作用机制。方法回顾性收集2015年1月至2018年12月台州市中心医院行手术切除并制成组织芯片的95例乳腺癌组织和其中20例乳腺癌患者的癌旁组织,采用免疫组化检测PGRN的表达并比较两组间的差异,分析PGRN表达与乳腺癌临床病理特征的关系以及乳腺癌组织中PGRN与EGFR表达的相关性;采用细胞计数试剂盒8(CCK-8)、细胞划痕和3D侵袭等实验检测EGFR抑制剂对PGRN激活剂溶血磷脂酸(LPA)诱导的乳腺癌MDA-MB-231细胞24、48、72 h后细胞存活以及24、48 h后细胞迁移和侵袭的逆转作用。结果与癌旁组织比较,乳腺癌组织中PGRN蛋白表达水平明显上调,差异有统计学意义(P<0.01)。不同年龄、不同肿瘤大小、不同组织学分级、是否淋巴结转移以及是否为三阴性的乳腺癌患者肿瘤组织中PGRN表达患者数比较差异均无统计学意义(均P>0.05)。相关性分析表明,乳腺癌组织中PGRN与EGFR表达呈正相关(r=0.353,P<0.01)。CCK-8法实验显示,EGFR抑制剂作用24、48、72 h后,LPA诱导的MDA-MB-231细胞存活率显著提高(均P<0.05)。细胞划痕实验显示,在24、48 h时,EGFR抑制剂显著抑制了LPA诱导的细胞迁移(均P<0.05)。3D侵袭实验显示,在第4天时,EGFR抑制剂显著抑制了LPA诱导的细胞侵袭(P<0.05)。结论PGRN在乳腺癌组织中明显上调,并与EGFR呈正相关;抑制EGFR的表达可显著抑制LPA诱导的细胞存活、迁移和侵袭能力,表明PGRN促进的乳腺癌发生、发展的作用机制可能与激活EG-FR相关。Objective To investigate the expression of progranulin(PGRN)in breast cancer and its relasion with epidermal growth factor receptor(EGFR).Methods Ninety five samples of breast cancer tissue and 20 samples of nontumorous tissue were collected in Taizhou Central Hospital from January 2015 to December 2018.The expression of PGRN was detected with immunohistochemistry in all samples,and the relationship of PGRN expression with clinical characteristics and EGFR expression of breast cancer were analyzed.The breast cancer MDA-MB-231 cells were treated with PGRN activator LPA,cell viability and invasion ability were measured by cell counting kit-8(CCK-8),wound healing and 3D invasion assays,respectively.The reversal effects of EGFR inhibitors on cell viability and invasion ability induced by LPA were also detected.Results The expression level of PGRN in breast cancer tissue were higher than that in nontumorous tissue(P<0.01).There was no significant difference in the expression level of PGRN in the tumor tissues with age,tumor size,histological grade,lymph node metastasis and tripe negative(all P>0.05).The expression of PGRN was positively corrected with EGFR expression in breast cancer tissues(r=0.353,P<0.01).CCK-8 assay showed that the EGFR inhibitor significantly reversed the survival of MDA-MB-231 cells induced by LPA treatment for 24 h,48 h and 72 h(all P<0.05).The Wound Healing assay showed that the EGFR inhibitor significantly inhibited cell migration induced by LPA treatment for 24 h and 48 h(both P<0.05).The 3D invasion assay showed that the EGFR inhibitor significantly inhibited cell invasion induced by LPA on d4(P<0.05).Conclusion PGRN expression is significantly upregulated in breast cancer tissues and is correlated with EGFR expression.Inhibiting EGFR can significantly reverse the cell survival,migration,and invasion induced by PGRN activator LPA.

关 键 词：乳腺癌 颗粒蛋白酶前体 表皮生长因子受体 侵袭 

分 类 号：R737.9[医药卫生—肿瘤]