上海交通大学学报（医学版）

›› 2012, Vol. 32 ›› Issue (12): 1615-.doi: 10.3969/j.issn.1674-8115.2012.12.020

• 论著（临床研究） • 上一篇    下一篇

支架蛋白IQGAP1在乳腺浸润性导管癌中的表达及对肿瘤细胞迁移的影响

金宇飚1, 田 丹2, 吕秀红1, 陈嘉薇1, 胡宏慧1   

  1. 1.上海交通大学附属第一人民医院病理科, 上海200080； 2.上海第一妇婴保健院病理科, 上海 200040
  • 出版日期:2012-12-28 发布日期:2012-12-31
  • 通讯作者: 陈嘉薇, 电子信箱: jiaweichen2000@sina.com。
  • 作者简介:金宇飚（1978—）, 男, 主治医师, 学士；电子信箱: fengyan9601103@yahoo.com.cn。

Expression of IQGAP1 in mammary ductal carcinoma and its effect on cancer cell migration

JIN Yu-biao1, TIAN Dan2, LÜ|Xiu-hong1, CHEN Jia-wei1, HU Hong-hui1   

  1. 1.Department of Pathology, the First People's Hospital, Shanghai Jiaotong University, Shanghai 200080, |China；2.Department of Pathology, Shanghai First Maternal and Infant Healthcare Hospital, Shanghai 200040, China
  • Online:2012-12-28 Published:2012-12-31

PDF (PC)

1248

摘要：

目的 探讨支架蛋白IQGAP1在乳腺浸润性导管癌中的表达及沉默IQGAP1表达对肿瘤细胞迁移能力的影响。方法 利用免疫组织化学染色和Western blotting技术检测IQGAP1蛋白在乳腺浸润性导管癌组织、癌旁组织以及良性乳腺病变组织中的表达；分析IQGAP1蛋白在乳腺浸润性导管癌组织中的表达与临床病理参数的关系。构建载有shRNA-IQGAP1的慢病毒表达载体，将其稳定转染高转移乳腺癌MDA-MB-435细胞，获得稳定抑制IQGAP1蛋白表达的细胞株（IQGAP1-shRNA组）及相应的空载细胞株（Vector组）、空白对照细胞株(Blank组)；运用基于Transwell系统的体外迁移实验观察沉默IQGAP1的表达对MDA-MB-435细胞迁移能力的影响。 结果 IQGAP1蛋白在乳腺浸润性导管癌组织中的阳性表达率为83.44%（136/163），与良性乳腺病变组织（32.14%，9/28）比较，差异具有统计学意义（P<0.01）；IQGAP1蛋白在癌旁组织中的阳性表达率(77.78%，63/81)与乳腺浸润性导管癌组织比较，差异无统计学意义（P>0.05）。163例乳腺浸润性导管癌中WHO分级为3级者IQGAP1蛋白表达为阴性、胞质阳性和胞膜阳性的例数分别为1、3和22，2级者分别为21、40和61；1级者分别为5、9和1，差异具有统计学意义（P<0.01）；IQGAP1蛋白的表达与肿瘤的大小有关（P<0.01），与淋巴结是否转移无关（P>0.05）。Blank组、Vector组和IQGAP1-shRNA组中穿过Transwell小室的平均细胞数分别为（294.3±16.3）、（287.7±16.9）和(93.5±7.6)个，IQGAP1-shRNA组显著低于其他两组（P<0.01）。结论 IQGAP1蛋白在乳腺浸润性导管癌组织中的表达明显高于良性乳腺病变组织；IQGAP1蛋白表达部位与肿瘤分化程度有关；IQGAP1蛋白在乳腺癌转移过程中起促进作用。

关键词: 乳腺导管癌, 具有IQ基序的GTP激酶活化蛋白, Transwell迁移实验

Abstract:

Objective To investigate the expression of IQ domain GTPase-activating protein (IQGAP1) in mammary ductal carcinoma, and explore the effect of IQGAP1 silencing on cancer cell migration. Methods The expression of IQGAP1 protein in mammary ductal carcinoma tissues, adjacent tissues of mammary ductal carcinoma and benign mammary lesion tissues was detected by immunohistochemical staining and Western blotting. The relationship between expression of IQGAP1 protein in mammary ductal carcinoma tissues and clinicopathological parameters was analysed. The lentivirus vector carrying shRNA-IQGAP1 was constructed, and the human mammary carcinoma MDA-MB-435 cells with high metastasis potential were stably transfected. MDA-MB-435 cells with stable silencing of the expression of IQGAP1 (IQGAP1-shRNA group), blank vector cells (Vector group) and blank control cells (Blank group) were obtained. The influence of IQGAP1 silencing on cancer cell migration was examined through in vitro cell migration test with Transwell system. Results There were significant differences between the positive expression rate of IQGAP1 protein in mammary ductal carcinoma tissues (83.44%, 136/163) and that in benign mammary lesion tissues (32.14%, 9/28)(P<0.01), while there was no significant difference between the positive expression rate of IQGAP1 protein in mammary ductal carcinoma tissues and that in adjacent tissues of mammary ductal carcinoma (77.78%，63/81)(P＞0.05). In 163 cases of mammary ductal carcinoma, the numbers of cases with negative expression of IQGAP1 protein, positive expression of IQGAP1 protein in cytoplasm and positive expression of IQGAP1 protein in membrane were 1, 3 and 22 respectively in those with grade 3 mammary ductal carcinoma; the numbers of cases were 21, 40 and 61 respectively in those with grade 2 mammary ductal carcinoma; the numbers of cases were 5, 9 and 1 respectively in those with grade 1 mammary ductal carcinoma; and there were significant differences among them （P＜0.01）. The expression of IQGAP1 protein was related to the size of tumor （P＜0.01）, but was no related to the lymph node metastasis （P＞0.05）. The mean numbers of cells penetrating Transwell chamber in Blank group, Vector group and IQGAP1-shRNA group were 294.3±16.3, 287.7±16.9 and 93.5±7.6 respectively, and the number in IQGAP1-shRNA group was significantly lower than those in the other two groups （P<0.01）. Conclusion The expression of IQGAP1 protein in mammary ductal carcinoma tissues is significantly higher than that in benign mammary lesion tissues, the location of IQGAP1 protein in mammary ductal carcinoma is associated with tumor differentiation, and IQGAP1 protein participates in tumor metastasis cascade.

Key words: mammary ductal carcinoma, IQ domain GTPase-activating protein, Transwell migration experiment