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Open Access 01-12-2013 | Research

Analysis of MAT3 gene expression in NSCLC

Authors: Shangen Zheng, Yuwen Du, Heying Chu, Xudong Chen, Ping Li, Yuanyuan Wang, Yunyun Ma, Huaqi Wang, Wenqiao Zang, Guojun Zhang, Guoqiang Zhao

Published in: Diagnostic Pathology | Issue 1/2013

Abstract

Background

Many studies have suggested different roles of Metastasis-associated protein 3 (MAT3) in different types of human cancers. However, expression of MAT3 in primary lung cancer and its relationship with clinicopathological factors have not been examined and the biological roles of MTA3 in lung cancer cells are still unclear.

Methods

The expression of MAT3 mRNA and protein were detected with quantitative real-time RT-PCR and immunohistochemical methods in 118 NSCLC samples and corresponding non-neoplastic samples. Survival curves were made with follow-up data. The relations of the prognosis with clinical and pathological characteristics were analyzed.

Results

The expression level of MAT3 mRNA and the positive rate of MAT3 protein were significantly higher in NSCLC samples than that in non-neoplastic samples, and in NSCLC samples with lymph node metastasis than that in NSCLC samples without lymph node metastasis (P < 0.01). MAT3 mRNA expression level was a risk factor of lymph node metastasis in patients with NSCLC (P = 0.006). There were significant differences in survival curves between lymph node metastatic group and non-metastatic group (P = 0.000), among groups of MAT3 positive and negative (P = 0.000), among groups of TNM stage I, II and III (P = 0.000) and among groups of tumor status T1, T2 and T3T4 (P = 0.000); but no statistical significance between male patients and female patients (P = 0.516), between ≥60 years old patients and <60 years old patients (P = 0.133), between histology types adenocarcinoma and squamous cell carcinoma (P = 0.865) and between well differentiation and moderate-poor differentiation (P = 0.134). The level of MAT3 mRNA (P = 0.000) and protein (P = 0.000) were risk factors of survival.

Conclusion

Our study showed that MAT3 over-expression in NSCLC tissue, and MAT3 mRNA level is a risk factor of lymph node metastasis. The level of MAT3 mRNA and protein were risk factors of survival in patients with NSCLC. It suggested that this antigen could be used as a simple and efficient parameter with which to identify high-risk patients.

Virtual slides

The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/5585901065503943.

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Pencil SD, Toh Y, Nicolson GL: Candidate metastasis-associated genes of the rat 13762NF mammary adenocarcinoma. Breast Cancer Res Treat. 1993, 25 (2): 165-174. 10.1007/BF00662141.CrossRefPubMed

Toh Y, Pencil SD, Nicolson GL: 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. 1994, 269 (37): 22958-22963.PubMed

Tong JK, Hassig CA, Schnitzler GR, Kingston RE, Schreiber SL, et al.: Chromatin deacetylation by an ATP-dependent nucleosome remodeling complex. Nature. 1998, 395 (6705): 917-921. 10.1038/27699.CrossRefPubMed

Xue Y, Wong J, Moreno GT, Young MK, Cote J, et al.: NURD, a novel complex with both ATP-dependent chromatin-remodeling and histone deacetylase activities. Mol Cell. 1998, 2 (6): 851-861. 10.1016/S1097-2765(00)80299-3.CrossRefPubMed

Wade PA, Gegonne A, Jones PL, Ballestar E, Aubry F, et al.: Mi-2 complex couples DNA methylation to chromatin remodelling and histone deacetylation. Nat Genet. 1999, 23 (1): 62-66. 10.1038/12664.CrossRefPubMed

Zhang Y, Ng HH, Erdjument-Bromage H, Tempst P, Bird A, et al.: Analysis of the NuRD subunits reveals a histone deacetylase core complex and a connection with DNA methylation. Genes Dev. 1999, 13 (15): 1924-1935. 10.1101/gad.13.15.1924.PubMedCentralCrossRefPubMed

Humphrey GW, Wang Y, Russanova VR, Hirai T, Qin J, et al.: Stable histone deacetylase complexes distinguished by the presence of SANT domain proteins CoREST/kiaa0071 and Mta-L1. J Biol Chem. 2001, 276 (9): 6817-6824. 10.1074/jbc.M007372200.CrossRefPubMed

Fujita N, Jaye DL, Kajita M, Geigerman C, Moreno CS, et al.: MTA3, a Mi-2/NuRD complex subunit, regulates an invasive growth pathway in breast cancer. Cell. 2003, 113 (2): 207-219. 10.1016/S0092-8674(03)00234-4.CrossRefPubMed

Dannenmann C, Shabani N, Friese K, Jeschke U, Mylonas I, et al.: The metastasis-associated gene MTA1 is upregulated in advanced ovarian cancer, represses ERbeta, and enhances expression of oncogenic cytokine GRO. Cancer Biol Ther. 2008, 7 (9): 1460-1467. 10.4161/cbt.7.9.6427.CrossRefPubMed

10.

Fujita N, Jaye DL, Geigerman C, Akyildiz A, Mooney MR, et al.: MTA3 and the Mi-2/NuRD complex regulate cell fate during B lymphocyte differentiation. Cell. 2004, 119 (1): 75-86. 10.1016/j.cell.2004.09.014.CrossRefPubMed

11.

Bruning A, Juckstock J, Blankenstein T, Makovitzky J, Kunze S, et al.: The metastasis-associated gene MTA3 is downregulated in advanced endometrioid adenocarcinomas. Histol Histopathol. 2010, 25 (11): 1447-1456.PubMed

12.

Zhang H, Stephens LC, Kumar R: Metastasis tumor antigen family proteins during breast cancer progression and metastasis in a reliable mouse model for human breast cancer. Clin Cancer Res. 2006, 12 (5): 1479-1486. 10.1158/1078-0432.CCR-05-1519.CrossRefPubMed

13.

Shi Y, Wu H, Zhang M, Ding L, Meng F, Fan X: Expression of the epithelial-mesenchymal transition-related proteins and their clinical significance in lung adenocarcinoma. Diagn Pathol. 2013, 8: 89-10.1186/1746-1596-8-89.PubMedCentralCrossRefPubMed

14.

Mylonas I, Bruning A: The metastasis-associated gene MTA3 is an independent prognostic parameter in uterine non-endometrioid carcinomas. Histopathol. 2012, 60 (4): 665-670. 10.1111/j.1365-2559.2011.04103.x.CrossRef

15.

Jemal A, Siegel R, Xu J: Ward E Cancer statistics, 2010. CA Cancer J Clin. 2010, 60 (5): 277-300. 10.3322/caac.20073.CrossRefPubMed

16.

Minna JD, Roth JA, Gazdar AF: Focus on lung cancer. Cancer Cell. 2002, 1 (1): 49-52. 10.1016/S1535-6108(02)00027-2.CrossRefPubMed

17.

Xiong Y, Bai Y, Leong N, Laughlin TS, Rothberg PG, Xu H, Nong L, Zhao J, Dong Y, Li T: Immunohistochemical detection of mutations in the epidermal growth factor receptor gene in lung adenocarcinomas using mutation-specific antibodies. Diagn Pathol. 2013, 8: 27-10.1186/1746-1596-8-27.PubMedCentralCrossRefPubMed

18.

Lu Q, Lu S, Huang L, Wang T, Wan Y, Zhou C, Zhang C, Zhang Z, Li X: The expression of V-ATPase is associated with drug resistance and pathology of non-small-cell lung cancer. Diagn Pathol. 2013, 8: 145-10.1186/1746-1596-8-145.PubMedCentralCrossRefPubMed

19.

Otto C, Csanadi A, Fisch P, Werner M, Kayser G: Molecular modeling and description of a newly characterized activating mutation of the EGFR gene in non-small cell lung cancer. Diagn Pathol. 2012, 7: 146-10.1186/1746-1596-7-146.PubMedCentralCrossRefPubMed

20.

Mishra SK, Talukder AH, Gururaj AE, Yang Z, Singh RR, Mahoney MG, Francí C, Vadlamudi RK, Kumar R: Upstream determinants of estrogen receptor-alpha regulation of metastatic tumor antigen 3 pathway. J Biol Chem. 2004, 279 (31): 32709-32715. 10.1074/jbc.M402942200.PubMedCentralCrossRefPubMed

21.

Fujita N, Kajita M, Taysavang P, Wade PA: Hormonal regulation of metastasis-associated protein 3 transcription in breast cancer cells. Mol Endocrinol. 2004, 18 (12): 2937-2949. 10.1210/me.2004-0258.CrossRefPubMed

22.

Chen Y, Miyazaki J, Nishizawa H, Kurahashi H, Leach R, Wang K: MTA3 regulates CGB5 and Snail genes in trophoblast. Biochem Biophys Res Commun. 2013, 433 (4): 379-384. 10.1016/j.bbrc.2013.02.102.PubMedCentralCrossRefPubMed

23.

Zhang H, Singh RR, Talukder AH, Kumar R: Metastatic tumor antigen 3 is a direct corepressor of the Wnt4 pathway. Genes Dev. 2006, 20 (21): 2943-2948. 10.1101/gad.1461706.PubMedCentralCrossRefPubMed

24.

Bagheri-Yarmand R, Talukder AH, Wang RA, Vadlamudi RK, Kumar R: Metastasis-associated protein 1 deregulation causes inappropriate mammary gland development and tumorigenesis. Development. 2004, 131 (14): 3469-3479. 10.1242/dev.01213.CrossRefPubMed

25.

Manavathi B, Singh K, Kumar R: MTA family of coregulators in nuclear receptor biology and pathology. Nucl Recept Signal. 2007, 5: e010-PubMedCentralPubMed

26.

Toh Y, Nicolson GL: The role of the MTA family and their encoded proteins in human cancers: molecular functions and clinical implications. Clin Exp Metastasis. 2009, 26 (3): 215-227. 10.1007/s10585-008-9233-8.CrossRefPubMed

Title: Analysis of MAT3 gene expression in NSCLC
Authors: Shangen Zheng
Yuwen Du
Heying Chu
Xudong Chen
Ping Li
Yuanyuan Wang
Yunyun Ma
Huaqi Wang
Wenqiao Zang
Guojun Zhang
Guoqiang Zhao
Publication date: 01-12-2013
Publisher: BioMed Central
Published in: Diagnostic Pathology / Issue 1/2013
Electronic ISSN: 1746-1596
DOI: https://doi.org/10.1186/1746-1596-8-166

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Analysis of MAT3 gene expression in NSCLC

Abstract

Background

Methods

Results

Conclusion

Virtual slides

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

Virtual slides

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