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摘要:
目的 探讨IQGAP1(IQ motif containing GTPase activating protein 1)在乳腺癌组织中的表达及意义。 方法 采用免疫组织化学链霉菌抗生物素蛋白-过氧化物酶(S-P法)染色法检测IQGAP1在乳腺癌组织及癌旁组织各110例中的蛋白表达水平。在正常乳腺上皮细胞系MCF-10A和乳腺癌细胞系MCF-7中开展IQGAP1表达调控实验。 结果 IQGAP1在乳腺癌组织中的表达高于癌旁正常乳腺组织(P=4.23×10-6)。IQGAP1的表达与浸润性导管癌的肿瘤大小(P=0.006)相关,在肿瘤>2 cm组明显高于肿瘤≤2 cm组。未发现与淋巴结转移(P=0.870),临床分期(P=0.278),ER状态(P=0.412)和PR状态(P=0.248)相关。IQGAP1高表达与乳腺癌术后无病生存时间(P=0.008)和总生存时间(P=0.029)相关。在乳腺癌细胞系MCF-7中,IQGAP1降低导致细胞增殖活性显著下降。 结论 IQGAP1可能在乳腺癌的发生发展过程中发挥重要作用。 Abstract:Objective To investigate the expression of IQGAP1 in breast cancer tissues and their tumor-adjacent normal tissues and the effect of IQGAP1 on the proliferation of breast cancer cells. Methods A total of 110 breast invasive ductal cancer (IDC) and its adjacent normal tissues specimens were screened for the expression of IQGAP1 with streptavidin-perosidase (S-P) immunohistochemistry. IQGAP1 gene expression was regulated in MCF-7 and MCF-10A cell line. Results The expression of IQGAP1 was higher in breast cancer tissues than in tumor-adjacent normal tissues (P = 4.23×10-6). The expression of IQGAP1 was correlated with tumor size, and was significantly higher in tumor > 2 cm than in tumor ≤ 2 cm (P = 0.006), but was not correlated with lymphnode metastasis (P = 0.870), clinical staging (P = 0.278), expression of estrogen receptor (ER) (P = 0.412) or progestogen receptor (PR) (P = 0.248) in IDC. IQGAP1 high expression was associated with poor progression free time (P = 0.008) and overall survival time (P = 0.029) among breast cancer patients. The proliferation rate of MCF-7 cells was significantly decreased after knocking down IQGAP1 expression. Conclusion IQGAP1 may play important roles in the development of breast cancer. -
Key words:
- IQGAP1 gene /
- Breast cancer /
- Tumor-adjacent normal tissue /
- Immunohistochemistry /
- Cell proliferation
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表 1 IQGAP1在乳腺癌及癌旁组织中的表达
Table 1. The expression of IQGAP1 in breast cancer and tumor-adjacent normal tissues
表 2 IQGAP1的表达与浸润性导管癌临床特点的关系
Table 2. Correlation of IQGAP1 expression with clinical characteristics of IDC
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[1] Coughlin SS, Ekwueme DU. Breast cancer as a global health concern[J]. Cancer Epidemiol, 2009, 33(5): 315-318. doi: 10.1016/j.canep.2009.10.003 [2] Noritake J, Watanabe T, Sato K, et al. IQGAP1: a key regulator of adhesion and migration[J]. J Cell Sci, 2005, 118: 2085-2092. doi: 10.1242/jcs.02379 [3] Meyer RD, Sacks DB, Rahimi N. IQGAP1-dependent signaling pathway regulates endothelial cell proliferation and angiogenesis[J]. PLoS ONE, 2008, 3(12): e3848. doi: 10.1371/journal.pone.0003848 [4] Wang Y, Wang A, Wang F, et al. IQGAP1 activates Tcf signal independent of Rac1 and Cdc42 in injury and repair of bronchial epithelial cells[J]. Exp Mol Pathol, 2008, 85: 122-128. doi: 10.1016/j.yexmp.2008.06.001 [5] Ren JG, Li Z, Sacks DB. IQGAP1 integrates Ca2+/calmodulin and B-Raf signaling[J]. J Biol Chem, 2008, 283: 22972-22982. doi: 10.1074/jbc.M804626200 [6] Wang Y, Wang M, Wang F, et al. IQGAP1 promotes cell proliferation and is involved in a phosphorylation-dependent manner in wound closure of bronchial epithelial cells[J]. Int J Mol Med, 2008, 22(1): 79-87. [7] Mataraza J M, Briggs M W, Li Z, et al. IQGAP1 promotes cell motility and invasion[J]. J Biol Chem, 2003, 278: 41237-41245. doi: 10.1074/jbc.M304838200 [8] Nabeshima K, Shimao Y, Inoue T, et al. Immunohistochemical analysis of IQGAP1 expression in human colorectal carcinomas: its overexpression in carcinomas and association with invasion fronts [J]. Cancer Lett, 2002, 176: 101-109. doi: 10.1016/S0304-3835(01)00742-X [9] Dong P, Nabeshima K, Nishimura N, et al. Overexpression and diffuse expression pattern of IQGAP1 at invasion fronts are independent prognostic parameters in ovarian carcinomas[J]. Cancer Lett, 2006, 243: 120-127. doi: 10.1016/j.canlet.2005.11.024 [10] Balenci L, Clarke I D, Dirks P B, et al. IQGAP1 protein specifies amplifying cancer cells in glioblastoma multiforme[J]. Cancer Res, 2006, 66: 9074-9082. doi: 10.1158/0008-5472.CAN-06-0761 [11] Johnson M, Sharma M, Henderson B R. IQGAP1 regulation and roles in cancer[J]. Cell Signal, 2009, 21(10): 1471-1478. doi: 10.1016/j.cellsig.2009.02.023 [12] Nakamura H, Fujita K, Nakagawa H, et al. Expression pattern of the scaffold protein IQGAP1 in lung cancer[J]. Oncol Rep, 2005, 13 (3): 427-431. [13] Jadeski L, Mataraza J M, Jeong H W, et al. IQGAP1 stimulates proliferation and enhances tumorigenesis of human breast epithelial cells[J]. J Biol Chem, 2008, 283(2): 1008-1017. doi: 10.1074/jbc.M708466200 [14] Li S, Wang Q, Chakladar A, et al. Gastric hyperplasia in mice lacking the putative Cdc42 effector IQGAP1[J]. Mol Cell Biol, 2000, 20: 697-701. doi: 10.1128/MCB.20.2.697-701.2000 [15] McDonald KL, O'Sullivan MG, Parkinson JF, et al. IQGAP1 and IGFBP2: valuable biomarkers for determining prognosis in glioma patients[J]. Neuropathol Exp Neurol, 2007, 66: 405-417. doi: 10.1097/nen.0b013e31804567d7 [16] Van 't Veer LJ, Dai H, Van de Vijver MJ, et al. Gene expression profiling predicts clinical outcome of breast cancer[J]. Nature, 2002, 415: 530-536. doi: 10.1038/415530a