Song Fangfang, Zhang Ling, Ji Ping, Zheng Hong, Zhao Yanrui, Zhang Wei, Chen Kexin
Department of Epidemiology and Biostatistics, Key Laboratory of Breast Cancer Prevention and Therapy, Ministry of Education, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tiyuan Bei, Hexi, Tianjin 300060, P.R. China.
Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Oncol Rep. 2015 Jun;33(6):2771-8. doi: 10.3892/or.2015.3905. Epub 2015 Apr 8.
Previous studies have characterized the migration and invasion inhibitory protein (MIIP) as a novel putative tumor-suppressor gene that regulates cell migration and invasion as well as the mitotic checkpoint. The MIIP gene is located on chromosome 1p36.22, a common site for deletion in many solid tumors including breast cancer. In the present study, we evaluated MIIP expression and allelic deletion to gain insight into the role of the MIIP gene in breast cancer. MIIP gene mRNA and protein expression was assessed in 86 matched breast cancer and adjacent normal tissues. Loss of heterogeneity (LOH) of the MIIP gene was determined using single-nucleotide polymorphism (SNP) and microsatellite (MS) markers in 149 breast carcinomas and the corresponding normal lymphocytes. The analysis revealed that the expression levels of MIIP mRNA and protein were downregulated in tumor specimens compared to those in corresponding adjacent tissues. Advanced clinical stage and tumor size >2 cm were associated with a decreased MIIP expression level. Twenty-six percent (37/142) of tumors were shown to have LOH at the MIIP locus by MS and SNP markers. Breast cancer patients with LOH at the SNP marker rs2295283 experienced shorter survival time. The attenuated expression and LOH of the MIIP gene may contribute to the poor prognosis of breast cancer, supporting a tumor-suppressing role of MIIP gene in the pathogenesis of this disease.
以往研究已将迁移和侵袭抑制蛋白（MIIP）鉴定为一种新型的假定肿瘤抑制基因，它可调节细胞迁移和侵袭以及有丝分裂检查点。MIIP基因位于1p36.22染色体上，这是包括乳腺癌在内的许多实体瘤中常见的缺失位点。在本研究中，我们评估了MIIP的表达和等位基因缺失情况，以深入了解MIIP基因在乳腺癌中的作用。在86对匹配的乳腺癌组织和癌旁正常组织中评估了MIIP基因的mRNA和蛋白表达。使用单核苷酸多态性（SNP）和微卫星（MS）标记，在149例乳腺癌及相应的正常淋巴细胞中检测了MIIP基因的杂合性缺失（LOH）。分析显示，与相应的癌旁组织相比，肿瘤标本中MIIP mRNA和蛋白的表达水平下调。临床晚期和肿瘤大小>2 cm与MIIP表达水平降低有关。通过MS和SNP标记显示，26%（37/142）的肿瘤在MIIP基因座处存在LOH。SNP标记rs2295283处存在LOH的乳腺癌患者生存时间较短。MIIP基因表达减弱和LOH可能导致乳腺癌预后不良，这支持了MIIP基因在该疾病发病机制中的肿瘤抑制作用。
