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http://dx.doi.org/10.7314/APJCP.2012.13.5.2385

ER81-shRNA Inhibits Growth of Triple-negative Human Breast Cancer Cell Line MDA-MB-231 In Vivo and in Vitro  

Chen, Yue (Department of Pathology, Kunming General Hospital)
Zou, Hong (Department of Pathology, Kunming General Hospital)
Yang, Li-Ying (Department of Pathology, Kunming General Hospital)
Li, Yuan (Department of Pathology, Kunming General Hospital)
Wang, Li (Department of Pathology, Kunming General Hospital)
Hao, Yan (Department of Pathology, Kunming General Hospital)
Yang, Ju-Lun (Department of Pathology, Kunming General Hospital)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.13, no.5, 2012 , pp. 2385-2392 More about this Journal
Abstract
The lack of effective treatment targets for triple-negative breast cancers make them unfitted for endocrine or HER2 targeted therapy, and their prognosis is poor. Transcription factor ER81, a downstream gene of the HER2, is highly expressed in breast cancer lines, breast atypical hyperplasia and primary breast cancers including triple-negative examples. However, whether and how ER81 affects breast cancer carcinogenesis have remained elusive. We here assessed influence on a triple-negative cell line. ER81-shRNA was employed to silence ER81 expression in the MDA-MB-231 cell line, and MTT, colony-forming assays, and flow cytometry were used to detect cell proliferation, colony-forming capability, cell cycle distribution, and cell apoptosis in vitro. MDA-MB-231 cells stably transfected with ER81-shRNA were inoculated into nude mice, and growth inhibition of the cells was observed in vivo. We found that ER81 mRNA and protein expression in MDA-MB-231 cells was noticeably reduced by ER81-shRNA, and that cell proliferation and clonality were decreased significantly. ER81-shRNA further increased cell apoptosis and the residence time in $G_0/G_1$ phase, while delaying tumor-formation and growth rate in nude mice. It is concluded that ER81 may play an important role in the progression of breast cancer and may be a potentially valuable target for therapy, especially for triple negative breast cancer.
Keywords
ER81; shRNA; breast cancer; triple-negative; gene therapy;
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1 Baert JL, Monte D, Musgrove EA, et al (1997). Expression of the PEA3 group of ETS-related transcription factors in human breast-cancer cells. Int J Cancer, 70, 590-7.   DOI
2 Bosc DG, Goueli BS, Janknecht R (2001). HER2/Neu-mediated activation of the ETS transcription factor ER81 and its target gene MMP-1. Oncogene, 20, 6215-24.   DOI
3 Bosc DG, Janknecht R (2002). Regulation of Her2/neu promoter activity by the ETS transcription factor, ER81. J Cell Biochem, 86, 174-83.   DOI
4 Brown TA, McKnight SL (1992). Specificities of protein-protein and protein-DNA interaction of GABP alpha and two newly defined ets-related proteins. Genes Dev, 6, 2502-12.   DOI
5 Cai C, Hsieh CL, Omwancha J, et al (2007). ETV1 is a novel androgen receptor-regulated gene that mediates prostate cancer cell invasion. Mol Endocrinol, 21, 1835-46.   DOI
6 Chen W, Yuan K, Tao ZZ, et al (2011). Deletion of Forkhead Box M1 transcription factor reduces malignancy in laryngeal squamous carcinoma cells. Asian Pac J Cancer Prev, 12, 1785-8.
7 Chi P, Chen Y, Zhang L, et al (2010). ETV1 is a lineage survival factor that cooperates with KIT in gastrointestinal stromal tumours. Nature, 467, 849-53.   DOI
8 Chung CH, Bernard PS, Perou CM (2002). Molecular portraits and the family tree of cancer. Nat Genet, 32, S533-40.   DOI
9 Clay CE, Namen AM, Atsumi G, et al (1999). Influence of J series prostaglandins on apoptosis and tumorigenesis of breast cancer cells. Carcinogenesis, 20, 1905-11.   DOI
10 Crawford HC, Fingleton B, Gustavson MD, et al (2001). The PEA3 subfamily of Ets transcription factors synergizes with beta-catenin-LEF-1 to activate matrilysin transcription in intestinal tumors. Mol Cell Biol, 21, 1370-83.   DOI
11 Cui JW, Li Y, Wang C, et al (2012). Knockdown of a proliferationinducing ligand (PRIL) suppresses the proliferation of gastric cancer cells. Asian Pac J Cancer Prev, 13, 633-6.   DOI
12 Dowdy SC, Mariani A, Janknecht R (2003). HER2/Neu- and TAK1-mediated up-regulation of the transforming growth factor beta inhibitor Smad7 via the ETS protein ER81. J Biol Chem, 278, 44377-84.   DOI
13 Fuchs B, Inwards C, Scully SP, et al (2004). hTERT Is highly expressed in Ewing's sarcoma and activated by EWS-ETS oncoproteins. Clin Orthop Relat Res, 426, 64-8.   DOI
14 Fuchs B, Inwards CY, Janknecht R (2003). Upregulation of the matrix metalloproteinase-1 gene by the Ewing's sarcoma associated EWS-ER81 and EWS-Fli-1 oncoproteins, c-Jun and p300. FEBS Lett, 553, 104-8.   DOI
15 Fuchs B, Inwards CY, Janknecht R (2004). Vascular endothelial growth factor expression is up-regulated by EWS-ETS oncoproteins and Sp1 and may represent an independent predictor of survival in Ewing's sarcoma. Clin Cancer Res, 10, 1344-53.   DOI
16 Galang CK, Muller WJ, Foos G, et al (2004). Changes in the expression of many Ets family transcription factors and of potential target genes in normal mammary tissue and tumors. J Biol Chem, 279, 11281-92.   DOI
17 Higashino F, Yoshida K, Fujinaga Y, et al (1993). Isolation of a cDNA encoding the adenovirus E1A enhancer binding protein: a new human member of the ets oncogene family. Nucleic Acids Res, 21, 547-53.   DOI
18 Goel A, Janknecht R (2003). Acetylation-mediated transcriptional activation of the ETS protein ER81 by p300, P/CAF, and HER2/Neu. Mol Cell Biol, 23, 6243-54.   DOI
19 Goueli BS, Janknecht R (2004). Upregulation of the catalytic telomerase subunit by the transcription factor ER81 and oncogenic HER2/Neu, Ras, or Raf. Mol Cell Biol, 24, 25-35.   DOI
20 Ha SA, Lee YS, Shin SM, et al (2009). Oncoprotein HCCR-1 expression in breast cancer is well correlated with known breast cancer prognostic factors including the HER2 overexpression, p53 mutation, and ER/PR status. BMC Cancer, 9, 51.   DOI
21 Holbro T, Civenni G, Hynes NE (2003). The ErbB receptors and their role in cancer progression. Exp Cell Res, 284, 99-110.   DOI   ScienceOn
22 Jane-Valbuena J, Widlund HR, Perner S, et al (2010). An oncogenic role for ETV1 in melanoma. Cancer Res, 70, 2075-84.   DOI
23 Janknecht R (1996). Analysis of the ERK-stimulated ETS transcription factor ER81. Mol Cell Biol, 16, 1550-6.   DOI
24 Janknecht R (2004). On the road to immortality: hTERT upregulation in cancer cells. FEBS Lett, 564, 9-13.   DOI
25 Janknecht R (2005). EWS-ETS oncoproteins: the linchpins of Ewing tumors. Gene, 363, 1-14.   DOI
26 Janknecht R, Ernst WH, Pingoud V, et al (1993). Activation of ternary complex factor Elk-1 by MAP kinases. EMBO J, 12, 5097-104.
27 Lv M, Li B, Li Y, et al (2011). Predictive role of molecular subtypes in response to neoadjuvant chemotherapy in breast cancer patients in Northeast China. Asian Pac J Cancer Prev, 12, 2411-7.
28 Jemal A, Bray F, Center MM, et al (2011). Global cancer statistics. CA Cancer J Clin, 61, 69-90.   DOI
29 Jeon IS, Davis JN, Braun BS, et al (1995). A variant Ewing's sarcoma translocation (7;22) fuses the EWS gene to the ETS gene ETV1. Oncogene, 10, 1229-34.
30 Lu WC, Liu YN, Kang BB, et al (2003). Trans-activation of heparanase promoter by ETS transcription factors. Oncogene, 22, 919-23.   DOI
31 Monte D, Baert JL, Laget MP, et al (1995). Transcription factors of the PEA3 group in mammary cancer. Ann Endocrinol, 56, 547-51 (in French).
32 Monte D, Coutte L, Baert JL, et al (1995). Molecular characterization of the ets-related human transcription factor ER81. Oncogene, 11, 771-9.
33 Netzer S, Leenders F, Dumont P, et al (2002). Ectopic expression of the ets transcription factor ER81 in transgenic mouse mammary gland enhances both urokinase plasminogen activator and stromelysin-1 transcription. Transgenic Res, 11, 123-31.   DOI
34 Papoutsopoulou S, Janknecht R (2000). Phosphorylation of ETS transcription factor ER81 in a complex with its coactivators CREB-binding protein and p300. Mol Cell Biol, 20, 7300-10.   DOI
35 Shepherd TG, L Kockeritz, MR Szrajber, et al. (2001). The pea3 subfamily ets genes are required for HER2/Neu-mediated mammary oncogenesis. Curr Biol, 11, 1739-48.   DOI
36 Shin SD, Bosc G, Ingle JN, et al (2008). Rcl is a novel ETV1/ ER81 target gene upregulated in breast tumors. J Cell Biochem, 105, 866-74.   DOI
37 Vageli D, Ioannou MG, Koukoulis GK (2009). Transcriptional activation of hTERT in breast carcinomas by the Her2-ER81-related pathway. Oncol Res, 17, 413-23.   DOI
38 Shin S, Kim TD, Jin F, et al (2009). Induction of prostatic intraepithelial neoplasia and modulation of androgen receptor by ETS variant 1/ETS-related protein 81. Cancer Res, 69, 8102-10.   DOI
39 Subik K, Lee JF, Baxter L, et al (2010). The Expression Patterns of ER, PR, HER2, CK5/6, EGFR, Ki-67 and AR by Immunohistochemical Analysis in Breast Cancer Cell Lines. Breast Cancer (Auckl), 4, 35-41.
40 Tomlins SA, Laxman B, Dhanasekaran SM, et al (2007). Distinct classes of chromosomal rearrangements create oncogenic ETS gene fusions in prostate cancer. Nature, 448, 595-9.   DOI
41 Wang Y, Wang L, Chen Y, et al (2011). ER81 Expression in Breast Cancers and Hyperplasia. Patholog Res Int, 2011, 980513.
42 Yu T, Hou F, Liu M, et al (2012). Norcantharidin antiangiogenesis activity possibly through an endothelial cell pathway in human colorectal cancer. Asian Pac J Cancer Prev, 13, 499-503.   DOI