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