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http://dx.doi.org/10.7314/APJCP.2014.15.14.5577

Short-Hairpin RNA-Mediated MTA2 Silencing Inhibits Human Breast Cancer Cell Line MDA-MB231 Proliferation and Metastasis  

Lu, Jun (Department of Pathology, Capital University, Beijing Chaoyang Hospital)
Jin, Mu-Lan (Department of Pathology, Capital University, Beijing Chaoyang Hospital)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.15, no.14, 2014 , pp. 5577-5582 More about this Journal
Abstract
Objective: To observe the effects of metastasis-associated tumor gene family 2 (MTA2) depletion on human breast cancer cell proliferation and metastasis. Methods: A short-hairpin RNA targeting MTA2 was chemically synthesized and transfected into a lentivirus to construct Lv-shMTA2 for infection into the MDA-MB231 human breast cancer cell line. At 48 hours after infection cells were harvested and mRNA and protein levels of MTA2 were determined by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting, respectively. Cell viability and metastasis were assessed by CCK-8, wound-healing assay and Transwell assay, respectively. In addition, a xenograft model of human breast cancer was constructed to investigate cancerous cell growth and capacity for metastasis. Results: After infection with Lv-shMTA2, mRNA and protein levels of MTA2 was significantly reduced (p<0.05) and MDA-MB231 cell proliferation and metastasis were inhibited (p<0.05). In addition, mean tumor size was smaller than that in control group nude mice (p<0.05) and numbers of metastatic deposits in lung were lower than in control group mice (p<0.05). Depletion of MTA2 affected MMP-2 and apoptosis-related protein expression. Conclusions: For the first time to our knowledge we showed that MTA2 depletion could significantly inhibit human breast cancer cell growth and metastasis, implying that MTA2 might be involved in the progression of breast cancer. The role of MTA2 in breast cancer growth and metastasis might be linked with regulation of matrix metalloproteinase and apoptosis.
Keywords
shRNA; MTA2; breast cancer; growth; metastasis;
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1 Armania N, Yazan LS, Ismail IS, et al (2013). Dillenia Suffruticosa extract inhibits proliferation of human breast cancer cell lines (MCF-7 and MDA-MB-231) via induction of G2/M arrest and apoptosis. Molecules, 18, 13320-39.   DOI
2 Cho KS, Elizondo LI, Boerkoel CF (2004). Advances in chromatin remodeling and human disease. Curr Opin Genet Dev, 14, 308-15.   DOI
3 Choi EJ, Kim GH (2013). O-desmethylangolensin inhibits the proliferation of human breast cancer MCF-7 cells by inducing apoptosis and promoting cell cycle arrest. Oncol Lett, 6, 1784-8.
4 Cui Y, Niu A, Pestell R, et al (2006). Metastasis-associated protein 2 is a repressor of estrogen receptor alpha whose overexpression leads to estrogen-independent growth of human breast cancer cells. Mol Endocrinol, 20, 2020-35.   DOI
5 Ding H, Wu YL, Wang YX, Zhu FF, et al (2014). Characterization of the microRNA expression profile of cervical squamous cell carcinoma metastases. Asian Pac J Cancer Prev, 15, 1675-9.   과학기술학회마을   DOI   ScienceOn
6 Erdogan B, Cicin I (2014). Medical treatment of breast cancer bone metastasis: from bisphosphonates to targeted drugs. Asian Pac J Cancer Prev, 15, 1503-10.   과학기술학회마을   DOI   ScienceOn
7 Fagan-Solis KD, Schneider SS, Pentecost BT, et al (2013). The RhoA pathway mediates MMP-2 and MMP-9-independent invasive behavior in a triple-negative breast cancer cell line. J Cell Biochem, 114, 1385-94.   DOI
8 Fearon ER (2003). Connecting estrogen receptor function, transcriptional repression, and E-cadherin expression in breast cancer. Cancer Cell, 3, 307-10.   DOI
9 Fidler IJ (1990). Critical factors in the biology of human cancer metastasis: twenty-eighth G.H.A. Clowes memorial award lecture. Cancer Res, 50, 6130-8.
10 Fujita N, Jaye DL, Kajita M, Geigerman C, Moreno CS, Wade PA (2003). MTA3, a Mi-2/NuRD complex subunit, regulates an invasive growth pathway in breast cancer. Cell, 113, 207-19.   DOI
11 Kumar R (2003). Another tie that binds the MTA family to breast cancer. Cell, 113, 142-3.   DOI
12 Kumar R, Wang RA, Bagheri-Yarmand R (2003). Emerging roles of MTA family members in human cancers. Semin Oncol, 30, 30-7.   DOI
13 Luo J, Su F, Chen D, Shiloh A, Gu W (2000). Deacetylation of p53 modulates its effect on cell growth and apoptosis. Nature, 408, 377-81.   DOI   ScienceOn
14 Roberts CW, Orkin SH (2004). The SWI/SNF complexchromatin and cancer. Nat Rev Cancer, 4, 133-42.   DOI   ScienceOn
15 Matsusue K, Takiguchi S, Toh Y, Kono A (2001). Characterization of mouse metastasis-associated gene 2: genomic structure, nuclear localization signal, and alternative potentials as transcriptional activator and repressor. DNA Cell Biol, 20, 603-11.   DOI
16 Puzovic V, Brcic I, Ranogajec I, Jakic-Razumovic J (2014). Prognostic values of ETS-1, MMP-2 and MMP-9 expression and co-expression in breast cancer patients. Neoplasma, 61, 439-47.   DOI
17 Radenkovic S, Konjevic G, Jurisic V, Karadzic K, Nikitovic M, Gopcevic K (2014). Values of MMP-2 and MMP-9 in tumor tissue of basal-like breast cancer patients. Cell Biochem Biophys, 68, 143-52.   DOI
18 Toh Y, Kuwano H, Mori M, Nicolson GL, Sugimachi K (1999). Overexpression of metastasis-associated MTA1 mRNA in invasive oesophageal carcinomas. Br J Cancer, 79, 1723-6.   DOI   ScienceOn
19 Toh Y, Oki E, Oda S et al (1997). Overexpression of the MTA1 gene in gastrointestinal carcinomas: correlation with invasion and metastasis. Int J Cancer, 74, 459-63.   DOI
20 Toh Y, Pencil SD, Nicolson GL (1994). A novel candidate metastasis-associated gene, mta1, differentially expressed in highly metastatic mammary adenocarcinoma cell lines. cDNA cloning, expression and protein analyses. J Biol Chem, 269, 22958-63.
21 Tong JK, Hassig CA, Schnitzler GR, Kingston RE, Schreiber SL (1998). Chromatin deacetylation by an ATP-dependent nucleosome remodelling complex. Nature, 395, 917-21.   DOI   ScienceOn
22 Shaukat U, Ismail M, Mehmood N (2013). Epidemiology, major risk factors and genetic predisposition for breast cancer in the Pakistani population. Asian Pac J Cancer Prev, 14, 5625-9.   과학기술학회마을   DOI
23 Wu JQ, Li YY, Ren JC, Zhao R, Zhou Y, Gao ES (2014). Induced abortion and breast cancer: results from a population-based case control study in china. Asian Pac J Cancer Prev, 15, 3635-40.   과학기술학회마을   DOI
24 Zhang H, Stephens LC, Kumar R (2006). Metastasis tumor antigen family proteins during breast cancer progression and metastasis in a reliable mouse model for human breast cancer. Clin Cancer Res, 12, 1479-86.   DOI
25 Zhou C, Ji J, Cai Q, et al (2013). MTA2 promotes gastric cancer cells invasion and is transcriptionally regulated by Sp1. Mol Cancer, 12, 102.   DOI