摘要
目的观察神经生长因子(NGF)受体TrkA和p75在乳腺肿瘤和不同乳腺癌细胞株的表达情况,分析它们与乳腺肿瘤的相关性及TrkA/p75比值对NGF诱导增殖效应的影响。方法采用免疫组化技术检测15例正常乳腺组织、28例乳腺良性肿瘤和62例乳腺恶性肿瘤中TrkA和p75的表达及乳腺癌细胞株MCF-7和SKBR3中NGF、TrkA和p75的表达,采用实时荧光定量PCR技术检测2种细胞株中TrkA和p75的mRNA表达水平,采用MTT检测2种细胞株对NGF诱导增殖的反应。结果 TrkA在乳腺恶性肿瘤中的表达高于乳腺良性肿瘤和正常乳腺组织(χ2=39.98,P<0.01);p75仅在正常乳腺的肌上皮细胞和结缔组织中高表达,随着肿瘤的恶性程度增高,p75的表达逐渐减少最终缺失(χ2=50.96,P<0.01);SKBR3乳腺癌细胞分泌的NGF,表达的TrkA和p75 mRNA及蛋白水平均高于MCF-7细胞(均P<0.05),并且SKBR3细胞表达的TrkA/p75比值高于MCF-7细胞(P<0.05);相对于空白对照组,NGF可诱导SKBR3和MCF-7细胞的增殖(均P<0.05),并在各时点,NGF对SKBR3细胞诱导的增殖率均高于MCF-7细胞(均P<0.05)。结论 TrkA和p75的表达与乳腺肿瘤的恶性程度有关,有可能作为乳腺癌治疗的分子靶点。
Objective To observe the expression of nerve growth factor receptors TrkA and p75 in breast neoplasms and breast cancer cell lines,and analyze the relationship between them and tumor development and the effect of TrkA/p75 on NGF-induced proliferation.Methods Immunohistochemical method was used to examine the expression of NGF,TrkA and p75 in 15 cases of normal breast tissues,28 cases of benign breast tumors,62 cases of breast cancers and two breast cancer cell lines MCF-7 and SKBR3.Real-time fluorescence quantitative PCR was used to detect TrkA and p75 mRNA expression,and MTT was used to measure proliferation of MCF-7 and SKBR3 cells.Results The expression of TrkA was higher in breast cancer than in benign breast tumor and normal breast tissues（χ2=39.98,P〈0.01）.The expression of p75 was detected only in the myoepithelial cells and the mammary connective tissues.With the increase of tumor malignancy,the expression of p75 was gradually reduced and finally abolished（χ2=50.96,P〈0.01）.The expression of NGF,TrkA,p75 and TrkA/p75 was increased in SKBR3 cells as compared with MCF-7 cells（P〈0.05）.As compared with control group,NGF could increase the proliferation of cells（P〈0.05）and cellular proliferation rate was higher in SKBR3 cells than in MCF-7 cells（P〈0.05）.Conclusion The expression of TrkA and p75 is related to the histological grading of breast tumors,and TrkA and p75 may provide the reference for the target treatment of breast cancer.
出处
《华中科技大学学报（医学版）》
CAS
CSCD
北大核心
2011年第4期423-428,共6页
Acta Medicinae Universitatis Scientiae et Technologiae Huazhong
基金
安徽省教育厅自然科学基金资助项目(No.KJ2010B119)
