Astrocyte elevated gene-1 and breast cancer (Review)

Wang,Chuan; Yang,Qifeng

doi:10.3892/ol.2011.268

Astrocyte elevated gene-1 and breast cancer (Review)

Authors:
- Chuan Wang
- Qifeng Yang
View Affiliations

Affiliations: Department of Breast Surgery, Qilu Hospital, Shandong University School of Medicine, Shandong 250012, P.R. China
Published online on: March 15, 2011 https://doi.org/10.3892/ol.2011.268
Pages: 399-405

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

Astrocyte elevated gene-1 (AEG-1), also known as MTDH and Lyric, is a novel gene that was first cloned by subtraction hybridization in 2002 and has recently been shown to play a role as a crucial oncogene that acts as a promoter of tumor malignancy. Overexpression and inhibition studies both in in vitro and in vivo models have partly shown the oncogenic roles of AEG-1 in a number of crucial aspects of tumor development and progression, including transformation, evasion of apoptosis, proliferation, cell survival, migration, invasion, metastasis, angiogenesis and chemoresistance through the activation of numerous signaling pathways, such as the nuclear factor κB, PI3K/AKT, Wnt/β-catenin and mitogen-activated protein kinase signaling pathways. However the potential roles of AEG-1, particularly in specific organs or tissues, such as breast tissue, require further clarification. Studies have found that in normal human breast tissue, AEG-1 is always expressed at low levels or is absent, while it is widely overexpressed in many breast cancer cell lines and breast tumors. The present review evaluates the current literature with regards to AEG-1 relative to breast cancer development and progression and highlights new perspectives relative to this molecule, indicating its potential to become a new target for the clinical treatment of breast cancer.

View Figures

View References

1	Krcova Z, Ehrmann J, Krejci V, Eliopoulos A and Kolar Z: Tpl-2/Cot and COX-2 in breast cancer. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 152:21–25. 2008. View Article : Google Scholar : PubMed/NCBI
2	Jezierska A and Motyl T: Matrix metalloproteinase-2 involvement in breast cancer progression: a mini-review. Med Sci Monit. 15:RA32–RA40. 2009.PubMed/NCBI
3	Gasparini G: Therapy of breast cancer with molecular targeting agents. Ann Oncol. 16:iv28–iv36. 2005. View Article : Google Scholar : PubMed/NCBI
4	Osborne C, Wilson P and Tripathy D: Oncogenes and tumor suppressor genes in breast cancer: potential diagnostic and therapeutic applications. Oncologist. 9:361–377. 2004. View Article : Google Scholar : PubMed/NCBI
5	Su ZZ, Kang DC, Chen YM, et al: Identification and cloning of human astrocyte genes displaying elevated expression after infection with HIV-1 or exposure to HIV-1 envelope glycoprotein by rapid subtraction hybridization, RaSH. Oncogene. 21:3592–3602. 2002. View Article : Google Scholar
6	Hu G, Wei Y and Kang Y: The multifaceted role of MTDH/AEG-1 in cancer progression. Clin Cancer Res. 15:5615–5620. 2009. View Article : Google Scholar : PubMed/NCBI
7	Li J, Zhang N, Song LB, et al: Astrocyte elevated gene-1 is a novel prognostic marker for breast cancer progression and overall patient survival. Clin Cancer Res. 14:3319–3326. 2008. View Article : Google Scholar : PubMed/NCBI
8	Kang D, Su Z, Sarkar D, Emdad L, Volsky D and Fisher P: Cloning and characterization of HIV-1-inducible astrocyte elevated gene-1, AEG-1. Gene. 353:8–15. 2005. View Article : Google Scholar : PubMed/NCBI
9	Brown DM and Ruoslahti E: Metadherin, a cell surface protein in breast tumors that mediates lung metastasis. Cancer Cell. 5:365–374. 2004. View Article : Google Scholar : PubMed/NCBI
10	Hu G, Chong R, Yang Q, et al: MTDH activation by 8q22 genomic gain promotes chemoresistance and metastasis of poor-prognosis breast cancer. Cancer Cell. 15:9–20. 2009. View Article : Google Scholar : PubMed/NCBI
11	Su Z: Customized rapid subtraction hybridization (RaSH) gene microarrays identify overlapping expression changes in human fetal astrocytes resulting from human immunodeficiency virus-1 infection or tumor necrosis factor-α treatment. Gene. 306:67–78. 2003.
12	Emdad L: Activation of the nuclear factor κB pathway by astrocyte elevated gene-1: implications for tumor progression and metastasis. Cancer Res. 66:1509–1516. 2006.
13	Thirkettle HJ, Girling J, Warren AY, et al: LYRIC/AEG-1 is targeted to different subcellular compartments by ubiquitinylation and intrinsic nuclear localization signals. Clin Cancer Res. 15:3003–3013. 2009. View Article : Google Scholar : PubMed/NCBI
14	Wu RC, Qin J, Hashimoto Y, et al: Regulation of SRC-3 (pCIP/ACTR/AIB-1/RAC-3/TRAM-1) coactivator activity by IκB kinase. Mol Cell Biol. 22:3549–3561. 2002.PubMed/NCBI
15	Lee SG, Su ZZ, Emdad L, Sarkar D and Fisher PB: Astrocyte elevated gene-1 (AEG-1) is a target gene of oncogenic Ha-ras requiring phosphatidylinositol 3-kinase and c-Myc. Proc Natl Acad Sci USA. 103:17390–17395. 2006. View Article : Google Scholar : PubMed/NCBI
16	Lee SG, Jeon HY, Su ZZ, et al: Astrocyte elevated gene-1 contributes to the pathogenesis of neuroblastoma. Oncogene. 28:2476–2484. 2009. View Article : Google Scholar : PubMed/NCBI
17	Thirkettle HJ, Mills IG, Whitaker HC and Neal DE: Nuclear LYRIC/AEG-1 interacts with PLZF and relieves PLZF-mediated repression. Oncogene. 28:3663–3670. 2009. View Article : Google Scholar : PubMed/NCBI
18	Sarkar D, Park ES, Emdad L, Lee SG, Su ZZ and Fisher PB: Molecular basis of nuclear factor-κB activation by astrocyte elevated gene-1. Cancer Res. 68:1478–1484. 2008.
19	Yoo BK, Emdad L, Su ZZ, et al: Astrocyte elevated gene-1 regulates hepatocellular carcinoma development and progression. J Clin Invest. 119:465–477. 2009. View Article : Google Scholar : PubMed/NCBI
20	Kikuno N, Shiina H, Urakami S, et al: Knockdown of astrocyte-elevated gene-1 inhibits prostate cancer progression through upregulation of FOXO3a activity. Oncogene. 26:7647–7655. 2007. View Article : Google Scholar : PubMed/NCBI
21	Khuda II, Koide N, Noman AS, et al: Astrocyte elevated gene-1 (AEG-1) is induced by lipopolysaccharide as toll-like receptor 4 (TLR4) ligand and regulates TLR4 signalling. Immunology. 128:e700–e706. 2009. View Article : Google Scholar : PubMed/NCBI
22	Lee SG, Su ZZ, Emdad L, Sarkar D, Franke TF and Fisher PB: Astrocyte elevated gene-1 activates cell survival pathways through PI3K-Akt signaling. Oncogene. 27:1114–1121. 2007.PubMed/NCBI
23	Yu C, Chen K, Zheng H, et al: Overexpression of astrocyte elevated gene-1 (AEG-1) is associated with esophageal squamous cell carcinoma (ESCC) progression and pathogenesis. Carcinogenesis. 30:894–901. 2009. View Article : Google Scholar : PubMed/NCBI
24	Emdad L, Lee SG, Su ZZ, et al: Astrocyte elevated gene-1 (AEG-1) functions as an oncogene and regulates angiogenesis. Proc Natl Acad Sci USA. 106:21300–21305. 2009. View Article : Google Scholar : PubMed/NCBI
25	Doerfler W, Hohlwey U, Müller K, Remus R, Heller H and Hertz J: Foreign DNA integration perturbations of the genome oncogenesis. Ann NY Acad Sci. 945:276–288. 2001. View Article : Google Scholar : PubMed/NCBI
26	Li J, Yang L, Song L, et al: Astrocyte elevated gene-1 is a proliferation promoter in breast cancer via suppressing transcriptional factor FOXO1. Oncogene. 28:3188–3196. 2009. View Article : Google Scholar : PubMed/NCBI
27	Liu JM, Yuan Y, Huan J and Shen ZY: Inhibition of breast and brain cancer cell growth by BCCIPalpha, an evolutionarily conserved nuclear protein that interacts with BRCA2. Oncogene. 20:336–345. 2001. View Article : Google Scholar : PubMed/NCBI
28	Meng XB, Lu HM and Shen ZY: BCCIP functions through p53 to regulate the expression of p21Waf1/Cip1. Cell Cycle. 3:1457–1462. 2004. View Article : Google Scholar : PubMed/NCBI
29	Ash S, Yang D and Britt D: LYRIC/AEG-1 overexpression modulates BCCIPα protein levels in prostate tumor cells. Biochem Biophys Res Commun. 371:333–338. 2008.PubMed/NCBI
30	Meng X, Fan J and Shen Z: Roles of BCCIP in chromosome stability and cytokinesis. Oncogene. 26:6253–6260. 2007. View Article : Google Scholar : PubMed/NCBI
31	Emdad L, Sarkar D, Su Z, et al: Astrocyte elevated gene-1: recent insights into a novel gene involved in tumor progression, metastasis and neurodegeneration. Pharmacol Ther. 114:155–170. 2007. View Article : Google Scholar : PubMed/NCBI
32	Kunnumakkara A, Anand P and Aggarwal B: Curcumin inhibits proliferation, invasion, angiogenesis and metastasis of different cancers through interaction with multiple cell signaling proteins. Cancer Lett. 269:199–225. 2008. View Article : Google Scholar
33	Qiao M, Sheng SJ and Pardee AB: Metastasis and Akt activation. Cell Cycle. 7:2991–2996. 2008. View Article : Google Scholar
34	Cao Y: Opinion: emerging mechanisms of tumour lymphangiogenesis and lymphatic metastasis. Nat Rev Cancer. 5:735–743. 2005. View Article : Google Scholar : PubMed/NCBI
35	Liu L, Wu J, Ying Z, et al: Astrocyte elevated gene-1 upregulates matrix metalloproteinase-9 and induces human glioma invasion. Cancer Res. 70:3750–3759. 2010. View Article : Google Scholar : PubMed/NCBI
36	Hanahan D and Weinberg RA: The hallmarks of cancer. Cell. 100:57–70. 2000. View Article : Google Scholar
37	Matsuo Y, Ochi N, Sawai H, et al: CXCL8/IL-8 and CXCL12/SDF-1α co-operatively promote invasiveness and angiogenesis in pancreatic cancer. Int J Cancer. 124:853–861. 2009.PubMed/NCBI
38	Kuwano T: Cyclooxygenase 2 is a key enzyme for inflammatory cytokine-induced angiogenesis. FASEB J. 18:300–310. 2004. View Article : Google Scholar : PubMed/NCBI
39	Marrogi A, Travis W, Welsh J, et al: Nitric oxide synthase, cyclooxygenase 2, and vascular endothelial growth factor in the angiogenesis of non-small cell lung carcinoma. Clin Cancer Res. 6:4739–4744. 2000.PubMed/NCBI
40	Liu H, Song X, Liu C, Xie L, Wei L and Sun R: Knockdown of astrocyte elevated gene-1 inhibits proliferation and enhancing chemo-sensitivity to cisplatin or doxorubicin in neuroblastoma cells. J Exp Clin Cancer Res. 28:192009. View Article : Google Scholar
41	Lerebours F, Vacher S, Andrieu C, et al: NF-kappa B genes have a major role in inflammatory breast cancer. BMC Cancer. 8:412008. View Article : Google Scholar : PubMed/NCBI
42	Yoo BK, Gredler R, Vozhilla N, et al: Identification of genes conferring resistance to 5-fluorouracil. Proc Natl Acad Sci USA. 106:12938–12943. 2009. View Article : Google Scholar : PubMed/NCBI
43	Yoo BK, Chen D, Su ZZ, et al: Molecular mechanism of chemoresistance by astrocyte elevated gene-1. Cancer Res. 70:3249–3258. 2010. View Article : Google Scholar : PubMed/NCBI
44	Kim DH, Mohapatra G, Bollen A, Waldman FM and Feuerstein BG: Chromosomal abnormalities in glioblastoma multiforme tumors and glioma cell lines detected by comparative genomic hybridization. Int J Cancer. 60:812–819. 1995. View Article : Google Scholar : PubMed/NCBI
45	Ried TJK, Holtgreve-Grez H, et al: Comparative genomic hybridization of formalin-fixed, paraffin-embedded breast tumors reveals different patterns of chromosomal gains and losses in fibroadenomas and diploid and aneuploid carcinomas. Cancer Res. 55:5415–5423. 1995.
46	Bergamaschi A, Kim YH, Wang P, et al: Distinct patterns of DNA copy number alteration are associated with different clinicopathological features and gene-expression subtypes of breast cancer. Genes Chromosomes Cancer. 45:1033–1040. 2006. View Article : Google Scholar
47	Warr T, Ward S, Burrows J, et al: Identification of extensive genomic loss and gain by comparative genomic hybridisation in malignant astrocytoma in children and young adults. Genes Chromosomes Cancer. 31:15–22. 2001. View Article : Google Scholar : PubMed/NCBI
48	Sarkar D, Emdad L, Lee SG, Yoo BK, Su ZZ and Fisher PB: Astrocyte elevated gene-1: far more than just a gene regulated in astrocytes. Cancer Res. 69:8529–8535. 2009. View Article : Google Scholar : PubMed/NCBI
49	Micalizzi DS, Farabaugh SM and Ford HL: Epithelial-mesenchymal transition in cancer: parallels between normal development and tumor progression. J Mammary Gland Biol Neoplasia. 15:117–134. 2010. View Article : Google Scholar : PubMed/NCBI
50	Trimboli AJ, Fukino K, de Bruin A, et al: Direct evidence for epithelial-mesenchymal transitions in breast cancer. Cancer Res. 68:937–945. 2008. View Article : Google Scholar : PubMed/NCBI
51	Radisky ES and Radisky DC: Matrix metalloproteinase-induced epithelial-mesenchymal transition in breast cancer. J Mammary Gland Biol Neoplasia. 15:201–212. 2010. View Article : Google Scholar : PubMed/NCBI
52	Britt D, Yang D, Flanagan D, et al: Identification of a novel protein, LYRIC, localized to tight junctions of polarized epithelial cells. Exp Cell Res. 300:134–148. 2004. View Article : Google Scholar : PubMed/NCBI
53	Itoh M and Bissell MJ: The organization of tight junctions in epithelia: implications for mammary gland biology and breast tumorigenesis. J Mammary Gland Biol Neoplasia. 8:449–462. 2003. View Article : Google Scholar : PubMed/NCBI
54	Ikenouchi J: Regulation of tight junctions during the epithelium-mesenchyme transition: direct repression of the gene expression of claudins/occludin by Snail. J Cell Sci. 116:1959–1967. 2003. View Article : Google Scholar : PubMed/NCBI