摘要目的 探讨葡萄糖转运蛋白1(glucose transporter 1,Glut-1)及其mRNA在正常乳腺组织、乳腺纤维腺病、乳腺纤维腺瘤和乳腺癌中的表达及其意义.方法 收集乳腺组织标本147例,其中乳腺浸润性导管癌92例、纤维腺瘤26例、腺病24例、正常乳腺组织5例,应用免疫组织化学EnVision法、Western blot以及RT-PCR分别定量检测不同病变组织中Glut-1蛋白及其mRNA表达水平.结果 在正常乳腺组织、乳腺腺病以及纤维腺瘤组织中难以检测到Glut-1阳性表达或仅呈轻微胞质着色.在乳腺癌组织中,Glut-1表达强度明显增高(P=0.0002),主要定位于瘤细胞膜,细胞质染色较淡.原发灶及转移灶中央的细胞Glut-1表达明显高于周边癌组织,转移灶Glut-1表达水平明显高于原发灶,浸润癌高于原位癌.Western blot定量分析结果显示,乳腺癌组织中Glut-1表达水平显著高于纤维腺瘤(P=0.001)和腺病(P=0.001),各病变组织间差异有统计学意义(P=0.0002).RT-PCR定量检测分析显示乳腺浸润性导管癌中Glut-1 mRNA的表达明显高于纤维腺瘤(P＜0.05)和腺病(P＜0.05),各病变组织间差异有统计学意义(P=0.0001).结论 乳腺癌组织中葡萄糖转运活性显著增高,Glut-1的表达水平与乳腺肿瘤的恶性程度、肿瘤细胞的浸润与转移密切相关;Glut-1高表达可作为细胞的恶性转化标志,并有望成为乳腺恶性肿瘤早期诊断、判断预后的一种新标记物及治疗的新靶点.

abstractsObjective To study the expression level and significance of glucose transporter 1(Glut1)in normal breast tissue,adenosis,adenoma and breast carcinoma.Methods A total of 147 cases of female breast tissue samples,including 92 cases of invasive ductal carcinoma,26 cases of breast fibroadenoma.24 cases of breast adenosis and 5 cases of normal breast tissues,were collected for quantitative detection of the expression of Glut-1 protein by immunohistochemistry(EnVision method)and Western blot,and its mRNA by reverse transeriptase-polymerase chain reaction(RT-PCR).Results In normal breast tissue and benign lesions of the breast,Glut-1 was undetectable or only weakly detectable in cytoplasm of ductal and acinar epithelia.In contrast,the intensity of Glut-1 staining was significantly higher in invasive ductal carcinomas (P=0.0002)with protein expression predominantly in cellular membrane and lesser in cytoplasm.Western blot and RT-PCR analyses showed that the expression of Glut-1 protein and mRNA were significantly increased in invasive ductal carcinoma than fibroadenoma(P=0.001 for protein;P＜0.05 for mRNA)and adenosis(P=0.001 for protein;P＜0.05 for mRNA).There was a significant difference among groups(P:0.0002 for protein;P=0.0001 for mRNA).Conclusions Glucose transport activity,as indicated by Glut-1 protein and its mRNA expression,significantly increases in breast carcinoma than non-cancerous lesions.The over-expression of Glut-1 in breast carcinoma is tightly coupled with tumor cell proliferation,invasion and metastasis,implying that Glut-1 may serve as a new marker in the early diagnosis and prognostication of breast malignancy as well as a new therapeutic target.