Altered expression and loss of heterozygosity of the migration and invasion inhibitory protein (MIIP) gene in breast cancer

Song,Fangfang; Zhang,Ling; Ji,Ping; Zheng,Hong; Zhao,Yanrui; Zhang,Wei; Chen,Kexin

doi:10.3892/or.2015.3905

Altered expression and loss of heterozygosity of the migration and invasion inhibitory protein (MIIP) gene in breast cancer

Authors:
- Fangfang Song
- Ling Zhang
- Ping Ji
- Hong Zheng
- Yanrui Zhao
- Wei Zhang
- Kexin Chen
View Affiliations

Affiliations: 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
Published online on: April 8, 2015 https://doi.org/10.3892/or.2015.3905
Pages: 2771-2778

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

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.

View Figures

View References

1	Parkin DM, Bray F, Ferlay J and Pisani P: Global cancer statistics, 2002. CA Cancer J Clin. 55:74–108. 2005. View Article : Google Scholar : PubMed/NCBI
2	Wooster R, Bignell G, Lancaster J, Swift S, Seal S, Mangion J, Collins N, Gregory S, Gumbs C and Micklem G: Identification of the breast cancer susceptibility gene BRCA2. Nature. 378:789–792. 1995. View Article : Google Scholar : PubMed/NCBI
3	Guan Y, Hata N, Kuga D, Yoshimoto K, Mizoguchi M, Shono T, Suzuki SO, Tahira T, Kukita Y, Higasa K, et al: Narrowing of the regions of allelic losses of chromosome 1p36 in meningioma tissues by an improved SSCP analysis. Int J Cancer. 122:1820–1826. 2008. View Article : Google Scholar
4	Zwahlen D, Tschan MP, Grob TJ, Peters UR, Fink D, Haenggi W, Altermatt HJ, Cajot JF, Tobler A, Fey MF, et al: Differential expression of p73 splice variants and protein in benign and malignant ovarian tumours. Int J Cancer. 88:66–70. 2000. View Article : Google Scholar : PubMed/NCBI
5	Song SW, Fuller GN, Zheng H and Zhang W: Inactivation of the invasion inhibitory gene IIp45 by alternative splicing in gliomas. Cancer Res. 65:3562–3567. 2005. View Article : Google Scholar : PubMed/NCBI
6	Song SW, Fuller GN, Khan A, Kong S, Shen W, Taylor E, Ramdas L, Lang FF and Zhang W: IIp45, an insulin-like growth factor binding protein 2 (IGFBP-2) binding protein, antagonizes IGFBP-2 stimulation of glioma cell invasion. Proc Natl Acad Sci USA. 100:13970–13975. 2003. View Article : Google Scholar : PubMed/NCBI
7	Wang Y, Wen J and Zhang W: MIIP, a cytoskeleton regulator that blocks cell migration and invasion, delays mitosis, and suppresses tumorogenesis. Curr Protein Pept Sci. 12:68–73. 2011. View Article : Google Scholar
8	Ji P, Smith SM, Wang Y, Jiang R, Song SW, Li B, Sawaya R, Bruner JM, Kuang J, Yu H, et al: Inhibition of gliomagenesis and attenuation of mitotic transition by MIIP. Oncogene. 29:3501–3508. 2010. View Article : Google Scholar : PubMed/NCBI
9	Song F, Ji P, Zheng H, Song F, Wang Y, Hao X, Wei Q, Zhang W and Chen K: Definition of a functional single nucleotide polymorphism in the cell migration inhibitory gene MIIP that affects the risk of breast cancer. Cancer Res. 70:1024–1032. 2010. View Article : Google Scholar : PubMed/NCBI
10	Wang Y, Yang D, Cogdell D, Hu L, Xue F, Broaddus R and Zhang W: Genomic characterization of gene copy-number aberrations in endometrial carcinoma cell lines derived from endometrioid-type endometrial adeno carcinoma. Technol Cancer Res Treat. 9:179–189. 2010. View Article : Google Scholar : PubMed/NCBI
11	Cairns P, Evron E, Okami K, Halachmi N, Esteller M, Herman JG, Bose S, Wang SI, Parsons R and Sidransky D: Point mutation and homozygous deletion of PTEN/MMAC1 in primary bladder cancers. Oncogene. 16:3215–3218. 1998. View Article : Google Scholar : PubMed/NCBI
12	Fujita T, Igarashi J, Okawa ER, Gotoh T, Manne J, Kolla V, Kim J, Zhao H, Pawel BR, London WB, et al: CHD5, a tumor suppressor gene deleted from 1p36.31 in neuroblastomas. J Natl Cancer Inst. 100:940–949. 2008. View Article : Google Scholar : PubMed/NCBI
13	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar
14	Chosdol K, Misra A, Puri S, Srivastava T, Chattopadhyay P, Sarkar C, Mahapatra AK and Sinha S: Frequent loss of heterozy-gosity and altered expression of the candidate tumor suppressor gene ‘FAT’ in human astrocytic tumors. BMC Cancer. 9:52009. View Article : Google Scholar
15	Schwarzenbach H, Muller V, Beeger C, Gottberg M, Stahmann N and Pantel K: A critical evaluation of loss of heterozygosity detected in tumor tissues, blood serum and bone marrow plasma from patients with breast cancer. Breast Cancer Res. 9:R662007. View Article : Google Scholar : PubMed/NCBI
16	Xu XM, Qian JC, Cai Z, Tang T, Wang P, Zhang KH, Deng ZL and Cai JP: DNA alterations of microsatellite DNA, p53, APC and K-ras in Chinese colorectal cancer patients. Eur J Clin Invest. 42:751–759. 2012. View Article : Google Scholar : PubMed/NCBI
17	Hanahan D and Weinberg RA: The hallmarks of cancer. Cell. 100:57–70. 2000. View Article : Google Scholar : PubMed/NCBI
18	Wu Y, Song SW, Sun J, Bruner JM, Fuller GN and Zhang W: IIp45 inhibits cell migration through inhibition of HDAC6. J Biol Chem. 285:3554–3560. 2010. View Article : Google Scholar :
19	Hata N, Yoshimoto K, Yokoyama N, Mizoguchi M, Shono T, Guan Y, Tahira T, Kukita Y, Higasa K, Nagata S, et al: Allelic losses of chromosome 10 in glioma tissues detected by quantitative single-strand conformation polymorphism analysis. Clin Chem. 52:370–378. 2006. View Article : Google Scholar : PubMed/NCBI
20	Cvetkovic D, Pisarcik D, Lee C, Hamilton TC and Abdollahi A: Altered expression and loss of heterozygosity of the LOT1 gene in ovarian cancer. Gynecol Oncol. 95:449–455. 2004. View Article : Google Scholar : PubMed/NCBI
21	Wegman PP, Marcus NJ, Malakkaran BP and Wingren S: Biological significance of allele specific loss of the p53 gene in breast carcinomas. Breast Cancer Res Treat. 118:15–20. 2009. View Article : Google Scholar