Additive effects of eukaryotic co‑expression plasmid carrying GRIM‑19 and LKB1 genes on breast cancer in vitro and in vivo Retraction in /10.3892/mmr.2021.12226

Zhang,Wei; Shao,Ying; Du,Ye; Geng,Wei; Jiang,Tong; Liu,Haipeng; Zhang,Duo

doi:10.3892/mmr.2015.4393

Additive effects of eukaryotic co‑expression plasmid carrying GRIM‑19 and LKB1 genes on breast cancer in vitro and in vivo

Retraction in: /10.3892/mmr.2021.12226

Authors:
- Wei Zhang
- Ying Shao
- Ye Du
- Wei Geng
- Tong Jiang
- Haipeng Liu
- Duo Zhang
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Affiliations: Department of Cosmetology Plastic Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China, Department of Breast Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China, Department of Gastrointestinal Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China, Department of Neurological Surgery, The Second Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
Published online on: September 30, 2015 https://doi.org/10.3892/mmr.2015.4393
Pages: 7665-7672

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Abstract

Gene associated with retinoid‑interferon‑induced mortality 19 (GRIM‑19) and the liver kinase B1 (LKB1) gene, two types of tumor suppressor gene, have been demonstrated to have important roles in breast carcinogenesis. The present study developed a dual expression plasmid that co‑expressed GRIM‑19 and LKB1, and evaluated the combined effects of the two genes against breast cancer in vitro and in vivo. Transfection with a plasmid for the simultaneous expression of GRIM‑19 and LKB1 (pGRIM19‑LKB1) into MCF‑7 breast cancer cells significantly inhibited the proliferation, colony formation, migration and invasion compared with the effects of transfection with either pGRIM‑19 or pLKB1 alone. Furthermore, transfection with pGRIM19‑LKB1 induced enhanced levels of apoptosis and cell cycle arrest at G0/G1 stage in MCF7 cells compared to the effects of pGRIM‑19 or pLKB1 alone. An in vivo experiment using an MCF‑7 xenograft tumor model demonstrated that intravenous injection of pGRIM19‑LKB1 had an enhanced effect on tumor growth inhibition compared to that of pGRIM‑19 or pLKB1 alone. In conclusion the findings of the present study suggested that transfection with eukaryotic plasmid for the simultaneous expression of GRIM‑19 and LKB1 more effectively suppressed the growth of breast cancer in vitro and in vivo, and may therefore have therapeutic potential for the treatment of human breast cancer.

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1	Siegel R, Naishadham D and Jemal A: Cancer statistics, 2013. CA Cancer J Clin. 63:11–30. 2013. View Article : Google Scholar : PubMed/NCBI
2	DeSantis C, Ma J, Bryan L and Jemal A: Breast cancer statistics, 2013. CA Cancer J Clin. 64:52–62. 2014. View Article : Google Scholar
3	Clark O, Botrel TE, Paladini L and Ferreira MB: Targeted therapy in triple-negative metastatic breast cancer: A systematic review and meta-analysis. Core Evid. 9:1–11. 2014. View Article : Google Scholar : PubMed/NCBI
4	Murphy IG, Dillon MF, Doherty AO, McDermott EW, Kelly G, O'Higgins N and Hill AD: Analysis of patients with false negative mammography and symptomatic breast carcinoma. J Surg Oncol. 96:457–463. 2007. View Article : Google Scholar : PubMed/NCBI
5	Fearnley IM, Carroll J, Shannon RJ, Runswick MJ, Walker JE and Hirst J: GRIM-19, a cell death regulatory gene product, is a subunit of bovine mitochondrial NADH: Ubiquinone oxidore-ductase (complex I). J Biol Chem. 276:38345–38348. 2001. View Article : Google Scholar : PubMed/NCBI
6	Huang G, Lu H, Hao A, Ng DC, Ponniah S, Guo K, Lufei C, Zeng Q and Cao X: GRIM-19, a cell death regulatory protein, is essential for assembly and function of mitochondrial complex I. Mol Cell Biol. 24:8447–8456. 2004. View Article : Google Scholar : PubMed/NCBI
7	Angell JE, Lindner DJ, Shapiro PS, Hofmann ER and Kalvakolanu DV: Identification of GRIM-19, a novel cell death-regulatory gene induced by the interferon-beta and retinoic acid combination, using a genetic approach. J Biol Chem. 275:33416–33426. 2000. View Article : Google Scholar : PubMed/NCBI
8	Nallar SC, Kalakonda S, Lindner DJ, Lorenz RR, Lamarre E, Weihua X and Kalvakolanu DV: Tumor-derived mutations in the gene associated with retinoid interferon-induced mortality (GRIM-19) disrupt its anti-signal transducer and activator of transcription 3 (STAT3) activity and promote oncogenesis. J Biol Chem. 288:7930–7941. 2013. View Article : Google Scholar : PubMed/NCBI
9	Lu Y, Fukuyama S, Yoshida R, Kobayashi T, Saeki K, Shiraishi H, Yoshimura A and Takaesu G: Loss of SOCS3 gene expression converts STAT3 function from anti-apoptotic to pro-apoptotic. J Biol Chem. 281:36683–36690. 2006. View Article : Google Scholar : PubMed/NCBI
10	Huang Y, Yang M, Yang H and Zeng Z: Upregulation of the GRIM-19 gene suppresses invasion and metastasis of human gastric cancer SGC-7901 cell line. Exp Cell Res. 316:2061–2070. 2010. View Article : Google Scholar : PubMed/NCBI
11	Huang G, Chen Y, Lu H and Cao X: Coupling mitochondrial respiratory chain to cell death: An essential role of mitochondrial complex I in the interferon-beta and retinoic acid-induced cancer cell death. Cell Death Differ. 14:327–337. 2007. View Article : Google Scholar
12	Hao H, Liu J, Liu G, Guan D, Yang Y, Zhang X, Cao X and Liu Q: Depletion of GRIM-19 accelerates hepatocellular carcinoma invasion via inducing EMT and loss of contact inhibition. J Cell Physiol. 227:1212–1219. 2012. View Article : Google Scholar
13	Zhou T, Chao L, Rong G, Wang C, Ma R and Wang X: Down-regulation of GRIM-19 is associated with STAT3 over-expression in breast carcinomas. Hum Pathol. 44:1773–1779. 2013. View Article : Google Scholar : PubMed/NCBI
14	Zhang W, Du Y, Jiang T, Geng W, Yuan J and Zhang D: Upregulation of GRIM-19 inhibits the growth and invasion of human breast cancer cells. Mol Med Rep. 12:2919–2925. 2015.PubMed/NCBI
15	Hemminki A, Markie D, Tomlinson I, Avizienyte E, Roth S, Loukola A, Bignell G, Warren W, Aminoff M, Höglund P, et al: A serine/threonine kinase gene defective in Peutz-Jeghers syndrome. Nature. 391:184–187. 1998. View Article : Google Scholar : PubMed/NCBI
16	Esteller M, Avizienyte E, Corn PG, Lothe RA, Baylin SB, Aaltonen LA and Herman JG: Epigenetic inactivation of LKB1 in primary tumors associated with the Peutz-Jeghers syndrome. Oncogene. 19:164–168. 2000. View Article : Google Scholar : PubMed/NCBI
17	Andrade-Vieira R, Xu Z, Colp P and Marignani PA: Loss of LKB1 expression reduces the latency of ErbB2-mediated mammary gland tumorigenesis, promoting changes in metabolic pathways. PLoS One. 8:e565672013. View Article : Google Scholar : PubMed/NCBI
18	Zhuang Z, Wang K, Cheng X, Qu X, Jiang B, Li Z, Luo J, Shao Z and Duan T: LKB1 inhibits breast cancer partially through repressing the Hedgehog signaling pathway. PLoS One. 8:e674312013. View Article : Google Scholar : PubMed/NCBI
19	Zhuang ZG, Di GH, Shen ZZ, Ding J and Shao ZM: Enhanced expression of LKB1 in breast cancer cells attenuates angio-genesis, invasion and metastatic potential. Mol Cancer Res. 4:843–849. 2006. View Article : Google Scholar : PubMed/NCBI
20	Linher-Melville K and Singh G: The transcriptional responsiveness of LKB1 to STAT-mediated signaling is differentially modulated by prolactin in human breast cancer cells. BMC cancer. 14:4152014. View Article : Google Scholar : PubMed/NCBI
21	Korsse SE, Peppelenbosch MP and van Veelen W: Targeting LKB1 signaling in cancer. Biochim Biophys Acta. 1835:194–210. 2013.PubMed/NCBI
22	Li L, Yu C, Ren J, Ye S, Ou W, Wang Y, Yang W, Zhong G, Chen X, Shi H, et al: Synergistic effects of eukaryotic coexpression plasmid carrying LKB1 and FUS1 genes on lung cancer in vitro and in vivo. J Cancer Res Clin Oncol. 140:895–907. 2014. View Article : Google Scholar : PubMed/NCBI
23	Duivenvoorden WC, Beatty LK, Lhotak S, Hill B, Mak I, Paulin G, Gallino D, Popovic S, Austin RC and Pinthus JH: Underexpression of tumour suppressor LKB1 in clear cell renal cell carcinoma is common and confers growth advantage in vitro and in vivo. Br J Cancer. 108:327–333. 2013. View Article : Google Scholar : PubMed/NCBI
24	Wang GM, Ren ZX, Wang PS, Su C, Zhang WX, Liu ZG, Zhang L, Zhao XJ and Chen G: Plasmid-based Stat3-specific siRNA and GRIM-19 inhibit the growth of thyroid cancer cells in vitro and in vivo. Oncol Rep. 32:573–580. 2014.PubMed/NCBI
25	Zhang L, Gao L, Li Y, Lin G, Shao Y, Ji K, Yu H, Hu J, Kalvakolanu DV and Kopecko DJ: Effects of plasmid-based Stat3-specific short hairpin RNA and GRIM-19 on PC-3M tumor cell growth. Clin Cancer Res. 14:559–568. 2008. View Article : Google Scholar : PubMed/NCBI
26	Wen LJ, Gao LF, Jin CS, Zhang HJ, Ji K, Yang JP, Zhao XJ, Wen MJ and Guan GF: Small interfering RNA survivin and GRIM-19 co-expression salmonella plasmid inhibited the growth of laryngeal cancer cells in vitro and in vivo. Int J Clin Exp Pathol. 6:2071–2081. 2013.PubMed/NCBI
27	Li X, Li Y, Hu J, Wang B, Zhao L, Ji K, Guo B, Yin D, Du Y, Kopecko DJ, et al: Plasmid-based E6-specific siRNA and co-expression of wild-type p53 suppresses the growth of cervical cancer in vitro and in vivo. Cancer Lett. 335:242–250. 2013. View Article : Google Scholar : PubMed/NCBI
28	Liu S, Zhang W, Liu K, Wang Y, Ji B and Liu Y: Synergistic effects of co-expression plasmid based ADAM10-specific siRNA and GRIM-19 on hepatocellular carcinoma in vitro and in vivo. Oncol Rep. 32:2501–2510. 2014.PubMed/NCBI
29	Yadav L, Puri N, Rastogi V, Satpute P, Ahmad R and Kaur G: Matrix metalloproteinases and cancer-roles in threat and therapy. Asian Pac J Cancer Prev. 15:1085–1091. 2014. View Article : Google Scholar
30	Abba M, Patil N and Allgayer H: MicroRNAs in the regulation of MMPs and metastasis. Cancers (Basel). 6:625–645. 2014. View Article : Google Scholar
31	Hadler-Olsen E, Winberg JO and Uhlin-Hansen L: Matrix metal-loproteinases in cancer: Their value as diagnostic and prognostic markers and therapeutic targets. Tumour Biol. 34:2041–2051. 2013. View Article : Google Scholar : PubMed/NCBI
32	Zhang M, Teng XD, Guo XX, Li ZG, Han JG and Yao L: Expression of tissue levels of matrix metalloproteinases and their inhibitors in breast cancer. Breast. 22:330–334. 2013. View Article : Google Scholar