Ezrin在高低转移潜能乳腺癌细胞中的表达及意义
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摘要
目的:探讨Ezrin蛋白对人高低转移潜能乳腺癌细胞亚系中的细胞增殖和侵袭能力的影响。
方法:利用免疫组化,逆转录聚合酶链反应(RT-PCR),免疫印(Western.Blot),放射免疫显像(RII)方法检测Ezrin蛋白在高低转移潜能乳腺癌细胞中的表达情况。采用四甲基偶氮唑蓝(MTT)法检测细胞增殖能力及黏附率。
结果:高转移潜能MDA-MB-435s细胞中Ezrin在基因和蛋白表达均显著高于低转移潜能MDA-MB-435s细胞。高转移潜能MDA-MB-435s细胞增殖能力和粘附率也都高于低转移潜能MDA-MB-435s细胞。131I标记的抗Ezrin抗体,在接种高转移潜能MDA-MB-435s细胞裸鼠肿瘤部位放射性浓聚强于接种低转移潜能MDA-MB-435s细胞裸鼠肿瘤部位放射性聚。
⑴免疫组化结果显示:在高转移潜能MDA-MB-435s细胞中Ezrin在胞浆胞膜呈强染色,呈强阳性,其平均光密度值为0.59±0.04;在低转移潜能乳腺癌细胞中细胞膜少量浅黄染色,呈弱阳性,其平均光密度值为0.12±0.02。图像分析和统计学结果表明,低转移潜能乳腺癌细胞与高转移潜能乳腺癌细胞相比较,染色减弱具有非常显著性差异(P<0.01)。
⑵RT-PCR分析结果显示:Ezrin mRNA在高转潜能移MDA-MB-435s细胞表达水平明显高于低转移潜能的MDA-MB-435s细胞,Ezrin在高转移潜能MDA-MB-435s细胞中表达的平均光密度值为0.69±0.07,在低转移潜能MDA-MB-435s细胞中表达的平均光密度值为0.15±0.03,两者比较,有非常显著性差异(P<0.01)。
⑶Western.Blot结果显示:高转移MDA-MB-435s细胞中Ezrin蛋白表达的平均光密度值为0.62±0.10 ,低转移MDA-MB-435s细胞中Ezrin蛋白表达的平均光密度值为0.13±0.04,高转移MDA-MB-435s细胞Ezrin蛋白表达水平亦明显高于低转移MDA-MB-435s细胞,有非常显著性差异(P<0.01)。
⑷31I标记抗Ezrin抗体对荷MDA-MB-435s细胞的裸鼠SPECT显像结果显示:接种高转移潜能细胞裸鼠肿瘤部位放射性浓聚较强,其平均光密度值为0.53±0.07;接种低转移潜能肿瘤部位放射性浓聚较弱,其平均光密度值为0.12±0.03,有非常显著性差异(P<0.01)。
结论:在不同转移潜能的乳腺癌MDA-MB-435s细胞中,Ezrin在高转移潜能乳腺癌细胞中的表达水平明显高于低转移潜能者。
Objective: The purpose of this experiment was to study the effect to cell proliferation and invasion about Ezrin proteinum in the two subgroups of human breast cancer cells,with highly-and lowly-metastatic potentiality.
Methods: The expression of Ezrin mRNA and protein were examined by Immune histochemistry,RT-PC,Western.blot and radioimmunoimaging method respectively.The proliferation and adhesion rate of the cells were examined by MTT.
Results: The expression of Ezrin at mRNA and protein levels were significantly higher in cells with highly-metastatic potentiality,the difference was significant (P<0.01). The proliferation and adhesion rate was higher in MDA-MB-435s cells with highly-metastatic potentiality ,the difference was significant (P<0.01). The images on 131I labeled Ezrin antibody showed that tumor location with highly-metastasis potentiality was of stronger radioactivity concentration, while tumor location with lowly-metastasis potentiality was of weaker radioactivity concentration, the difference was significant (P<0.01).
⑴The result of immune histochemistry indicated: within the breast cancer MDA-MB-435s cell line with highly-metastasis potentiality, Nucl-Cyto-Mem was strongly dyed ,the average optical value is 0.59±0.04,while within the breast cancer MDA-MB-435s cell line with lowly-metastasis, membrane was slightly dyed in light yellow ,the average optical value is 0.12±0.02. Image analysis and statistic results indicated that comparing the breast cancer with lowly-metastasis potentiality with the breast cancer with highly-metastasis potentiality, dying moderation was of very significant difference(P<0.01)
⑵The RT-PCR results indicated: the expression of Ezrin’s mRNA in breast cancer MDA-MB-435s cells with highly-metastasis potentiality was obviously higher than that in cells with lowly-metastasis potentiality. The average optical density value in the breast cancer cells with highly-metastasis potentiality is 0.69±0.07,and The average optical density value in the breast cancer MDA-MB-435s cells with lowly-metastasis potentiality is 0.15±0.03,there were significant differences (P<0.01)
⑶Results of Western.Blot indicated: The Ezrin protein average optical density value in the breast cancer MDA-MB-435s cells with highly-metastasis potentiality is 0.62±0.10, and The average optical density value in the breast cancer MDA-MB-435s cells with lowly-metastasis potentiality is 0.13±0.04, Comparing the average optical density value in the expression level of breast cancer MDA-MB-435s cells with highly-metastasis potentiality and that in cells with lowly-metastasis potentiality, there were very significant differences (P<0.01)
⑷SPECT images of 131I labeled Ezrin antibody in nude mice bearing human breast cancer indicated: the images showed that tumor location with highly-metastasis potentiality was of stronger radioactivity concentration, The average optical density value is 0.53±0.07;while tumor location with lowly-metastasis potentiality was of weaker radioactivity concentration.,the average optical density value is 0.12±0.03.The difference was very significant (P<0.01).
Conclusions: The expression of Ezrin in breast cancer MDA-MB-435s cells with highly-metastasis potentiality was obviously higher than that in cells with lowly-metastasis potentiality.
方法:利用免疫组化,逆转录聚合酶链反应(RT-PCR),免疫印(Western.Blot),放射免疫显像(RII)方法检测Ezrin蛋白在高低转移潜能乳腺癌细胞中的表达情况。采用四甲基偶氮唑蓝(MTT)法检测细胞增殖能力及黏附率。
结果:高转移潜能MDA-MB-435s细胞中Ezrin在基因和蛋白表达均显著高于低转移潜能MDA-MB-435s细胞。高转移潜能MDA-MB-435s细胞增殖能力和粘附率也都高于低转移潜能MDA-MB-435s细胞。131I标记的抗Ezrin抗体,在接种高转移潜能MDA-MB-435s细胞裸鼠肿瘤部位放射性浓聚强于接种低转移潜能MDA-MB-435s细胞裸鼠肿瘤部位放射性聚。
⑴免疫组化结果显示:在高转移潜能MDA-MB-435s细胞中Ezrin在胞浆胞膜呈强染色,呈强阳性,其平均光密度值为0.59±0.04;在低转移潜能乳腺癌细胞中细胞膜少量浅黄染色,呈弱阳性,其平均光密度值为0.12±0.02。图像分析和统计学结果表明,低转移潜能乳腺癌细胞与高转移潜能乳腺癌细胞相比较,染色减弱具有非常显著性差异(P<0.01)。
⑵RT-PCR分析结果显示:Ezrin mRNA在高转潜能移MDA-MB-435s细胞表达水平明显高于低转移潜能的MDA-MB-435s细胞,Ezrin在高转移潜能MDA-MB-435s细胞中表达的平均光密度值为0.69±0.07,在低转移潜能MDA-MB-435s细胞中表达的平均光密度值为0.15±0.03,两者比较,有非常显著性差异(P<0.01)。
⑶Western.Blot结果显示:高转移MDA-MB-435s细胞中Ezrin蛋白表达的平均光密度值为0.62±0.10 ,低转移MDA-MB-435s细胞中Ezrin蛋白表达的平均光密度值为0.13±0.04,高转移MDA-MB-435s细胞Ezrin蛋白表达水平亦明显高于低转移MDA-MB-435s细胞,有非常显著性差异(P<0.01)。
⑷31I标记抗Ezrin抗体对荷MDA-MB-435s细胞的裸鼠SPECT显像结果显示:接种高转移潜能细胞裸鼠肿瘤部位放射性浓聚较强,其平均光密度值为0.53±0.07;接种低转移潜能肿瘤部位放射性浓聚较弱,其平均光密度值为0.12±0.03,有非常显著性差异(P<0.01)。
结论:在不同转移潜能的乳腺癌MDA-MB-435s细胞中,Ezrin在高转移潜能乳腺癌细胞中的表达水平明显高于低转移潜能者。
Objective: The purpose of this experiment was to study the effect to cell proliferation and invasion about Ezrin proteinum in the two subgroups of human breast cancer cells,with highly-and lowly-metastatic potentiality.
Methods: The expression of Ezrin mRNA and protein were examined by Immune histochemistry,RT-PC,Western.blot and radioimmunoimaging method respectively.The proliferation and adhesion rate of the cells were examined by MTT.
Results: The expression of Ezrin at mRNA and protein levels were significantly higher in cells with highly-metastatic potentiality,the difference was significant (P<0.01). The proliferation and adhesion rate was higher in MDA-MB-435s cells with highly-metastatic potentiality ,the difference was significant (P<0.01). The images on 131I labeled Ezrin antibody showed that tumor location with highly-metastasis potentiality was of stronger radioactivity concentration, while tumor location with lowly-metastasis potentiality was of weaker radioactivity concentration, the difference was significant (P<0.01).
⑴The result of immune histochemistry indicated: within the breast cancer MDA-MB-435s cell line with highly-metastasis potentiality, Nucl-Cyto-Mem was strongly dyed ,the average optical value is 0.59±0.04,while within the breast cancer MDA-MB-435s cell line with lowly-metastasis, membrane was slightly dyed in light yellow ,the average optical value is 0.12±0.02. Image analysis and statistic results indicated that comparing the breast cancer with lowly-metastasis potentiality with the breast cancer with highly-metastasis potentiality, dying moderation was of very significant difference(P<0.01)
⑵The RT-PCR results indicated: the expression of Ezrin’s mRNA in breast cancer MDA-MB-435s cells with highly-metastasis potentiality was obviously higher than that in cells with lowly-metastasis potentiality. The average optical density value in the breast cancer cells with highly-metastasis potentiality is 0.69±0.07,and The average optical density value in the breast cancer MDA-MB-435s cells with lowly-metastasis potentiality is 0.15±0.03,there were significant differences (P<0.01)
⑶Results of Western.Blot indicated: The Ezrin protein average optical density value in the breast cancer MDA-MB-435s cells with highly-metastasis potentiality is 0.62±0.10, and The average optical density value in the breast cancer MDA-MB-435s cells with lowly-metastasis potentiality is 0.13±0.04, Comparing the average optical density value in the expression level of breast cancer MDA-MB-435s cells with highly-metastasis potentiality and that in cells with lowly-metastasis potentiality, there were very significant differences (P<0.01)
⑷SPECT images of 131I labeled Ezrin antibody in nude mice bearing human breast cancer indicated: the images showed that tumor location with highly-metastasis potentiality was of stronger radioactivity concentration, The average optical density value is 0.53±0.07;while tumor location with lowly-metastasis potentiality was of weaker radioactivity concentration.,the average optical density value is 0.12±0.03.The difference was very significant (P<0.01).
Conclusions: The expression of Ezrin in breast cancer MDA-MB-435s cells with highly-metastasis potentiality was obviously higher than that in cells with lowly-metastasis potentiality.
引文
[1] Fidler IJ. Tumor heterogeneity and the biology of cancer invasion and metastasis[J]. Cancer Res,1978;38(9):2651-2660.
[2] Chambers AF,Macdonald IC,Schmidt EE. Steps in tumor metastasis new concepts from intravital videmicroscopy Cancer Metastasis Rev, 1995,14:279-301.
[3]王磊,李大强,侯意枫,等.乳腺癌不同肺转移潜能细胞株表达差异蛋白及其临床意义[J].中国癌症杂志,2006,16(9):706-709.
[4]叶丽虹,吴莲英,郭威,等.乳腺癌MCF-7细胞系转移亚克隆的筛选及其生物学特性研究[J].中华医学杂志,2006,86(1):61-65.
[5]刘宇欣,郑杰,方伟岗,等.具有不同转移潜能的前列腺癌细胞亚系的分离鉴定[J].中华病理学杂志,1999;28(5):361-364.
[6]陈翔,杨彤涛,马保安,等.不同转移潜能骨肉瘤细胞株的建立与生物学特性的分析[J].第四军医大学学报,2005,25(21):1992-1995..
[7]牛坚,李向农,韩泽广.人胰腺癌不同转移潜能细胞株的分离筛选和鉴定.胰腺病学,2007,7(6):375-377.
[8]朱伟勇,郑杰,方伟岗,等.具有不同转移潜能的肺癌细胞亚系的分离鉴定[J].中华病理学杂志, 1995;24(3):136-138.
[9]谢汉平,江露,陈家祺.新鲜羊膜移植治疗眼表疾病的临床评价.第三军医大学学报,2000 ,22(9) :889.
[10]陈长宏,王曙光,李大江,等.腹膜浸润筛选模型体外筛选胆管癌细胞不同转移性亚群[J].重庆医学,2002,31(11):1039-1040.
[11]谭晓杰,侯建国,贺松琴,等.采用体外侵袭实验分离侵袭性人原代肾细胞癌细胞[J].第二军医大学学报,2006,27(3):318-321.
[12]宋波,金锡御,潘进洪,等.以体外侵袭力构建高转移膀胱癌细胞亚系[J].中华泌尿外科杂志,1998,19(8):387-390.
[13] Seton-Rogers SE,Lu Y,Hines LM,et a1.Cooperation of the ErbB2 receptor and transforming growth factor beta in induction of migration and invasion in mammary epithelial cells[J].Proc Natl Acad Sci USA,2004,101:1257-1262.
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[2] Chambers AF,Macdonald IC,Schmidt EE. Steps in tumor metastasis new concepts from intravital videmicroscopy Cancer Metastasis Rev, 1995,14:279-301.
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[4]叶丽虹,吴莲英,郭威,等.乳腺癌MCF-7细胞系转移亚克隆的筛选及其生物学特性研究[J].中华医学杂志,2006,86(1):61-65.
[5]刘宇欣,郑杰,方伟岗,等.具有不同转移潜能的前列腺癌细胞亚系的分离鉴定[J].中华病理学杂志,1999;28(5):361-364.
[6]陈翔,杨彤涛,马保安,等.不同转移潜能骨肉瘤细胞株的建立与生物学特性的分析[J].第四军医大学学报,2005,25(21):1992-1995..
[7]牛坚,李向农,韩泽广.人胰腺癌不同转移潜能细胞株的分离筛选和鉴定.胰腺病学,2007,7(6):375-377.
[8]朱伟勇,郑杰,方伟岗,等.具有不同转移潜能的肺癌细胞亚系的分离鉴定[J].中华病理学杂志, 1995;24(3):136-138.
[9]谢汉平,江露,陈家祺.新鲜羊膜移植治疗眼表疾病的临床评价.第三军医大学学报,2000 ,22(9) :889.
[10]陈长宏,王曙光,李大江,等.腹膜浸润筛选模型体外筛选胆管癌细胞不同转移性亚群[J].重庆医学,2002,31(11):1039-1040.
[11]谭晓杰,侯建国,贺松琴,等.采用体外侵袭实验分离侵袭性人原代肾细胞癌细胞[J].第二军医大学学报,2006,27(3):318-321.
[12]宋波,金锡御,潘进洪,等.以体外侵袭力构建高转移膀胱癌细胞亚系[J].中华泌尿外科杂志,1998,19(8):387-390.
[13] Seton-Rogers SE,Lu Y,Hines LM,et a1.Cooperation of the ErbB2 receptor and transforming growth factor beta in induction of migration and invasion in mammary epithelial cells[J].Proc Natl Acad Sci USA,2004,101:1257-1262.
[1]马小斌,王西京. Ezrin在肿瘤转移中的作用及机制研究进展[J].国际外科学杂志,2007,34(1):50-54.
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