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World Journal of Surgical Oncology

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Open Access 01-12-2013 | Research

Expression of metallothionein and Nrf2 pathway genes in lung cancer and cancer-surrounding tissues

Authors: Gui-You Liang, Sheng-Xun Lu, Gang Xu, Xing-Da Liu, Jian Li, Deng-Shen Zhang

Published in: World Journal of Surgical Oncology | Issue 1/2013

Abstract

Background

Nuclear factor (erythroid-derived 2)-like (Nrf)2 and metallothionein have been implicated in carcinogenesis. This study investigated the expression of Nrf2 and of Nrf2-targeted genes (NQO1 and GCLC) and the genes for the metallothionein (MT) isoforms (MT-1A and MT-2A) in human lung cancer and cancer-surrounding tissues.

Methods

Surgically removed lung cancer samples (n = 80) and cancer-surrounding tissues (n = 38) were collected from Zunyi Medical College Hospital, China. Total RNA was extracted, purified, and used for real-time reverse transcription-PCR analysis of interested genes.

Results

Expression of the Nrf2-targed genes NQO1 and GCLC tended to be higher (30 to 60%) in lung cancers, but was not significantly different from that in peri-cancer tissues. By contrast, expression of the genes for M)-1A, MT-2A, and the metal transcription factor MTF-1 were three-fold to four-fold lower in lung cancers.

Conclusion

In surgical samples of lung cancer, MT expression was generally downregulated, whereas Nrf2 expression tended to be upregulated. These changes could play an integral role in lung carcinogenesis.

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Müller T, Hengstermann A: Nrf2: friend and foe in preventing cigarette smoking-dependent lung disease. Chem Res Toxicol. 2012, 25: 1805-1824. 10.1021/tx300145n.CrossRefPubMed

Pi J, Freeman ML, Yamamoto M: Nrf2 in toxicology and pharmacology: the good, the bad and the ugly?. Toxicol Appl Pharmacol. 2010, 244: 1-3. 10.1016/j.taap.2010.01.005.PubMedCentralCrossRefPubMed

Cherian MG, Jayasurya A, Bay BH: Metallothioneins in human tumors and potential roles in carcinogenesis. Mutat Res. 2003, 533: 201-209. 10.1016/j.mrfmmm.2003.07.013.CrossRefPubMed

Klaassen CD, Liu J, Choudhuri S: Metallothionein: an intracellular protein to protect against cadmium toxicity. Ann Rev Pharmacol Toxicol. 1999, 39: 267-294. 10.1146/annurev.pharmtox.39.1.267.CrossRef

Jacob ST, Majumder S, Ghoshal K: Suppression of metallothionein-I/II expression and its probable molecular mechanisms. Environ Health Perspect. 2002, 110 (Suppl 5): 827-830.PubMedCentralCrossRefPubMed

Kanda M, Nomoto S, Okamura Y, Nishikawa Y, Sugimoto H, Kanazumi N, Takeda S, Nakao A: Detection of metallothionein 1G as a methylated tumor suppressor gene in human hepatocellular carcinoma using a novel method of double combination array analysis. Int J Oncol. 2009, 35: 477-483.CrossRefPubMed

Tao X, Zheng JM, Xu AM, Chen XF, Zhang SH: Downregulated expression of metallothionein and its clinicopathological significance in hepatocellular carcinoma. Hepatol Res. 2007, 37: 820-827. 10.1111/j.1872-034X.2007.00113.x.CrossRefPubMed

Dziegiel P, Jeleń M, Muszczyńska B, Maciejczyk A, Szulc A, Podhorska-Okołów M, Cegielski M, Zabel M: Role of metallothionein expression in non-small cell lung carcinomas. RoczAkad Med Bialymst. 2004, 49 (Suppl 1): 43-45.

Zhong S, Fields CR, Su N, Pan YX, Robertson KD: Pharmacologic inhibition of epigenetic modifications, coupled with gene expression profiling, reveals novel targets of aberrant DNA methylation and histone deacetylation in lung cancer. Oncogene. 2007, 26: 2621-2634. 10.1038/sj.onc.1210041.CrossRefPubMed

10.

Tsou JA, Galler JS, Wali A, Ye W, Siegmund KD, Groshen S, Laird PW, Turla S, Koss MN, Pass HI, Laird-Offringa IA: DNA methylation profile of 28 potential marker loci in malignant mesothelioma. Lung Cancer. 2007, 58: 220-230. 10.1016/j.lungcan.2007.06.015.PubMedCentralCrossRefPubMed

11.

Theocharis S, Karkantaris C, Philipides T, Agapitos E, Gika A, Margeli A, Kittas C, Koutselinis A: Expression of metallothionein in lung carcinoma: correlation with histological type and grade. Histopathology. 2002, 40: 143-151. 10.1046/j.1365-2559.2002.01325.x.CrossRefPubMed

12.

Faller WJ, Rafferty M, Hegarty S, Gremel G, Ryan D, Fraga MF, Esteller M, Dervan PA, Gallagher WM: Metallothionein 1E is methylated in malignant melanoma and increases sensitivity to cisplatin-induced apoptosis. Melanoma Res. 2010, 20: 392-400.PubMed

13.

Ferrario C, Lavagni P, Gariboldi M, Miranda C, Losa M, Cleris L, Formelli F, Pilotti S, Pierotti MA, Greco A: Metallothionein 1G acts as an oncosupressor in papillary thyroid carcinoma. Lab Invest. 2008, 88: 474-481. 10.1038/labinvest.2008.17.CrossRefPubMed

14.

Henrique R, Jerónimo C, Hoque MO, Nomoto S, Carvalho AL, Costa VL, Oliveira J, Teixeira MR, Lopes C, Sidransky D: MT1G hypermethylation is associated with higher tumor stage in prostate cancer. Cancer Epidemiol Biomarkers Prev. 2005, 14: 1274-1278. 10.1158/1055-9965.EPI-04-0659.CrossRefPubMed

15.

Waalkes MP, Diwan BA, Weghorst CM, Ward JM, Rice JM, Cherian MG, Goyer RA: Further evidence of the tumor-suppressive effects of cadmium in the B6C3F1 mouse liver and lung: late stage vulnerability of tumors to cadmium and the role of metallothionein. J Pharmacol Exp Ther. 1993, 266: 1656-1663.PubMed

16.

Waalkes MP, Diwan BA, Rehm S, Ward JM, Moussa M, Cherian MG, Goyer RA: Down-regulation of metallothionein expression in human and murine hepatocellular tumors: association with the tumor-necrotizing and antineoplastic effects of cadmium in mice. J Pharmacol Exp Ther. 1996, 277: 1026-1033.PubMed

17.

Majumder S, Roy S, Kaffenberger T, Wang B, Costinean S, Frankel W, Bratasz A, Kuppusamy P, Hai T, Ghoshal K, Jacob ST: Loss of metallothionein predisposes mice to diethylnitrosamine-induced hepatocarcinogenesis by activating NF-kappaB target genes. Cancer Res. 2010, 70: 10265-10276. 10.1158/0008-5472.CAN-10-2839.PubMedCentralCrossRefPubMed

18.

Klaassen CD, Reisman SA: Nrf2 the rescue: effects of the antioxidative/electrophilic response on the liver. Toxicol Appl Pharmacol. 2010, 244: 57-65. 10.1016/j.taap.2010.01.013.PubMedCentralCrossRefPubMed

19.

MacLeod AK, McMahon M, Plummer SM, Higgins LG, Penning TM, Igarashi K, Hayes JD: Characterization of the cancer chemopreventive NRF2-dependent gene battery in human keratinocytes: demonstration that the KEAP1-NRF2 pathway, and not the BACH1-NRF2 pathway, controls cytoprotection against electrophiles as well as redox-cycling compounds. Carcinogenesis. 2009, 30: 1571-1580. 10.1093/carcin/bgp176.PubMedCentralCrossRefPubMed

20.

Lau A, Villeneuve NF, Sun Z, Wong PK, Zhang DD: Dual roles of Nrf2 in cancer. Pharmacol Res. 2008, 58: 262-270. 10.1016/j.phrs.2008.09.003.PubMedCentralCrossRefPubMed

Title: Expression of metallothionein and Nrf2 pathway genes in lung cancer and cancer-surrounding tissues
Authors: Gui-You Liang
Sheng-Xun Lu
Gang Xu
Xing-Da Liu
Jian Li
Deng-Shen Zhang
Publication date: 01-12-2013
Publisher: BioMed Central
Published in: World Journal of Surgical Oncology / Issue 1/2013
Electronic ISSN: 1477-7819
DOI: https://doi.org/10.1186/1477-7819-11-199

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Expression of metallothionein and Nrf2 pathway genes in lung cancer and cancer-surrounding tissues

Abstract

Background

Methods

Results

Conclusion

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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