Skip to main content
Erschienen in: Targeted Oncology 2/2012

01.06.2012 | Original Research

Expression of metastasis-associated protein 2 (MTA2) might predict proliferation in non-small cell lung cancer

verfasst von: Shu-Li Liu, Yang Han, Yong Zhang, Cheng-Yao Xie, En-Hua Wang, Yuan Miao, Hai-Ying Li, Hong-Tao Xu, Shun-Dong Dai

Erschienen in: Targeted Oncology | Ausgabe 2/2012

Einloggen, um Zugang zu erhalten

Abstract

Metastatic tumor antigen 2 (MTA2) is a member of the MTA family that is closely associated with tumor progression and metastasis. In this study, the expression profile of MTA2 in 223 cases of non-small cell lung cancer (NSCLC) tissues and two lung cancer cell lines was investigated. Interestingly, we found MTA2, which was believed to have nuclear distribution only, was distributed in both nucleus and cytoplasm in normal and cancer cells. Nuclear MTA2 expression was detected in 148 cases of NSCLC (66.4 %), and was correlated with advanced TNM stages (p = 0.023), tumor size (p = 0.036), and lymph node metastasis (p = 0.004). Besides, the Ki-67 proliferation index was significantly higher in nuclear MTA2-positive tumors than in nuclear MTA2-negative tumors (r = 0.538, p = 0.006). However, there was no significant difference in cytoplasmic MTA2 status by age, gender, tumor stage, histology, grade, lymph node metastasis, and Ki-67 proliferation index. Univariate analysis revealed nuclear MTA2 expression was correlated with poor overall survival (p = 0.035), whereas there was a nonsignificant trend in the same direction for cytoplasmic MTA2 (p = 0.134). Multivariate Cox regression analysis revealed the overexpression of nuclear and cytoplasmic MTA2 not to be independent factors predictive of poor disease outcome. Our data suggested that MTA2 might play roles in both the nucleus and cytoplasm in the progression of NSCLC.
Literatur
1.
Zurück zum Zitat Ganti AK, Huang CH, Klein MA, Keefe S, Kelley MJ (2011) Lung cancer management in 2010. Oncology (Williston Park, NY) 25:64–73 Ganti AK, Huang CH, Klein MA, Keefe S, Kelley MJ (2011) Lung cancer management in 2010. Oncology (Williston Park, NY) 25:64–73
2.
Zurück zum Zitat Liotta LA, Steeg PS, Stetler-Stevenson WG (1991) Cancer metastasis and angiogenesis: an imbalance of positive and negative regulation. Cell 64:327–336PubMedCrossRef Liotta LA, Steeg PS, Stetler-Stevenson WG (1991) Cancer metastasis and angiogenesis: an imbalance of positive and negative regulation. Cell 64:327–336PubMedCrossRef
3.
Zurück zum Zitat Sleeman J, Steeg PS (2010) Cancer metastasis as a therapeutic target. Eur J Cancer 46:1177–1180PubMedCrossRef Sleeman J, Steeg PS (2010) Cancer metastasis as a therapeutic target. Eur J Cancer 46:1177–1180PubMedCrossRef
4.
Zurück zum Zitat Yaguchi M, Wada Y, Toh Y, Iguchi H, Kono A, Matsusue K et al (2005) Identification and characterization of the variants of metastasis-associated protein 1 generated following alternative splicing. Biochim Biophys Acta 1732:8–14PubMed Yaguchi M, Wada Y, Toh Y, Iguchi H, Kono A, Matsusue K et al (2005) Identification and characterization of the variants of metastasis-associated protein 1 generated following alternative splicing. Biochim Biophys Acta 1732:8–14PubMed
5.
Zurück zum Zitat Bowen NJ, Fujita N, Kajita M, Wade PA (2004) Mi-2/NuRD: multiple complexes for many purposes. Biochim Biophys Acta 1677:52–57PubMed Bowen NJ, Fujita N, Kajita M, Wade PA (2004) Mi-2/NuRD: multiple complexes for many purposes. Biochim Biophys Acta 1677:52–57PubMed
6.
Zurück zum Zitat Kumar R, Wang RA, Bagheri-Yarmand R (2003) Emerging roles of MTA family members in human cancers. Semin Oncol 30:30–37PubMedCrossRef Kumar R, Wang RA, Bagheri-Yarmand R (2003) Emerging roles of MTA family members in human cancers. Semin Oncol 30:30–37PubMedCrossRef
7.
Zurück zum Zitat Toh Y, Kuninaka S, Endo K, Oshiro T, Ikeda Y, Nakashima H et al (2000) Molecular analysis of a candidate metastasis-associated gene, MTA1: possible interaction with histone deacetylase 1. J Exp Clin Cancer Res 19:105–111PubMed Toh Y, Kuninaka S, Endo K, Oshiro T, Ikeda Y, Nakashima H et al (2000) Molecular analysis of a candidate metastasis-associated gene, MTA1: possible interaction with histone deacetylase 1. J Exp Clin Cancer Res 19:105–111PubMed
8.
Zurück zum Zitat Moon WS, Chang K, Tarnawski AS (2004) Overexpression of metastatic tumor antigen 1 in hepatocellular carcinoma: relationship to vascular invasion and estrogen receptor-alpha. Hum Pathol 35:424–429PubMedCrossRef Moon WS, Chang K, Tarnawski AS (2004) Overexpression of metastatic tumor antigen 1 in hepatocellular carcinoma: relationship to vascular invasion and estrogen receptor-alpha. Hum Pathol 35:424–429PubMedCrossRef
9.
Zurück zum Zitat Hamatsu T, Rikimaru T, Yamashita Y, Aishima S, Tanaka S, Shirabe K et al (2003) The role of MTA1 gene expression in human hepatocellular carcinoma. Oncol Rep 10:599–604PubMed Hamatsu T, Rikimaru T, Yamashita Y, Aishima S, Tanaka S, Shirabe K et al (2003) The role of MTA1 gene expression in human hepatocellular carcinoma. Oncol Rep 10:599–604PubMed
10.
Zurück zum Zitat Sasaki H, Moriyama S, Nakashima Y, Kobayashi Y, Yukiue H, Kaji M et al (2002) Expression of the MTA1 mRNA in advanced lung cancer. Lung Cancer 35:149–154PubMedCrossRef Sasaki H, Moriyama S, Nakashima Y, Kobayashi Y, Yukiue H, Kaji M et al (2002) Expression of the MTA1 mRNA in advanced lung cancer. Lung Cancer 35:149–154PubMedCrossRef
11.
Zurück zum Zitat Toh Y, Kuwano H, Mori M, Nicolson GL, Sugimachi K (1999) Overexpression of metastasis-associated MTA1 mRNA in invasive oesophageal carcinomas. Br J Cancer 79:1723–1726PubMedCrossRef Toh Y, Kuwano H, Mori M, Nicolson GL, Sugimachi K (1999) Overexpression of metastasis-associated MTA1 mRNA in invasive oesophageal carcinomas. Br J Cancer 79:1723–1726PubMedCrossRef
12.
Zurück zum Zitat Hofer MD, Kuefer R, Varambally S, Li H, Ma J, Shapiro GI et al (2004) The role of metastasis-associated protein 1 in prostate cancer progression. Cancer Res 64:825–829PubMedCrossRef Hofer MD, Kuefer R, Varambally S, Li H, Ma J, Shapiro GI et al (2004) The role of metastasis-associated protein 1 in prostate cancer progression. Cancer Res 64:825–829PubMedCrossRef
13.
Zurück zum Zitat Iguchi H, Imura G, Toh Y, Ogata Y (2000) Expression of MTA1, a metastasis-associated gene with histone deacetylase activity in pancreatic cancer. Int J Oncol 16:1211–1214PubMed Iguchi H, Imura G, Toh Y, Ogata Y (2000) Expression of MTA1, a metastasis-associated gene with histone deacetylase activity in pancreatic cancer. Int J Oncol 16:1211–1214PubMed
14.
Zurück zum Zitat Jang KS, Paik SS, Chung H, Oh YH, Kong G (2006) MTA1 overexpression correlates significantly with tumor grade and angiogenesis in human breast cancers. Cancer Sci 97:374–379PubMedCrossRef Jang KS, Paik SS, Chung H, Oh YH, Kong G (2006) MTA1 overexpression correlates significantly with tumor grade and angiogenesis in human breast cancers. Cancer Sci 97:374–379PubMedCrossRef
15.
Zurück zum Zitat Wang S, Qi Y, Zhang J, Zhang Q, Li H, Qiu X (2010) Expression and significance of MTA2 in non-small cell lung cancer. Zhongguo fei ai za zhi Chinese J Lung Cancer 13:777–780 Wang S, Qi Y, Zhang J, Zhang Q, Li H, Qiu X (2010) Expression and significance of MTA2 in non-small cell lung cancer. Zhongguo fei ai za zhi Chinese J Lung Cancer 13:777–780
16.
Zurück zum Zitat Goldstraw P, Crowley J, Chansky K, Giroux DJ, Groome PA, Rami-Porta R et al (2007) The IASLC Lung Cancer Staging Project: proposals for the revision of the TNM stage groupings in the forthcoming (seventh) edition of the TNM Classification of malignant tumours. J Thorac Oncol 2:706–714PubMedCrossRef Goldstraw P, Crowley J, Chansky K, Giroux DJ, Groome PA, Rami-Porta R et al (2007) The IASLC Lung Cancer Staging Project: proposals for the revision of the TNM stage groupings in the forthcoming (seventh) edition of the TNM Classification of malignant tumours. J Thorac Oncol 2:706–714PubMedCrossRef
17.
Zurück zum Zitat Travis WD, Brambilla E, Muller-Hermelink HK, Harris CC (2004) World health organization classification of tumours: pathology and genetics of tumours of the lung, pleura, thymus and heart. IARC Press, Lyon Travis WD, Brambilla E, Muller-Hermelink HK, Harris CC (2004) World health organization classification of tumours: pathology and genetics of tumours of the lung, pleura, thymus and heart. IARC Press, Lyon
18.
Zurück zum Zitat Dai SD, Wang Y, Jiang GY, Zhang PX, Dong XJ, Wei Q et al (2010) Kaiso is expressed in lung cancer: its expression and localization is affected by p120ctn. Lung Cancer 67:205–215PubMedCrossRef Dai SD, Wang Y, Jiang GY, Zhang PX, Dong XJ, Wei Q et al (2010) Kaiso is expressed in lung cancer: its expression and localization is affected by p120ctn. Lung Cancer 67:205–215PubMedCrossRef
19.
Zurück zum Zitat Dai SD, Wang Y, Miao Y, Zhao Y, Zhang Y, Jiang GY et al (2009) Cytoplasmic Kaiso is associated with poor prognosis in non-small cell lung cancer. BMC Cancer 9:178PubMedCrossRef Dai SD, Wang Y, Miao Y, Zhao Y, Zhang Y, Jiang GY et al (2009) Cytoplasmic Kaiso is associated with poor prognosis in non-small cell lung cancer. BMC Cancer 9:178PubMedCrossRef
20.
Zurück zum Zitat Cui Y, Niu A, Pestell R, Kumar R, Curran EM, Liu Y 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. Molecular Endocrinol 20:2020–2035CrossRef Cui Y, Niu A, Pestell R, Kumar R, Curran EM, Liu Y 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. Molecular Endocrinol 20:2020–2035CrossRef
21.
Zurück zum Zitat Manavathi B, Singh K, Kumar R (2007) MTA family of coregulators in nuclear receptor biology and pathology. Nucl Recept Signal 5:e010PubMed Manavathi B, Singh K, Kumar R (2007) MTA family of coregulators in nuclear receptor biology and pathology. Nucl Recept Signal 5:e010PubMed
22.
Zurück zum Zitat Luo J, Su F, Chen D, Shiloh A, Gu W (2000) Deacetylation of p53 modulates its effect on cell growth and apoptosis. Nature 408:377–381PubMedCrossRef Luo J, Su F, Chen D, Shiloh A, Gu W (2000) Deacetylation of p53 modulates its effect on cell growth and apoptosis. Nature 408:377–381PubMedCrossRef
23.
Zurück zum Zitat Chakraborty S, Ganti AK, Marr A, Batra SK (2010) Lung cancer in women: role of estrogens. Expert Rev Respir Med 4:509–518PubMedCrossRef Chakraborty S, Ganti AK, Marr A, Batra SK (2010) Lung cancer in women: role of estrogens. Expert Rev Respir Med 4:509–518PubMedCrossRef
24.
Zurück zum Zitat Zhang Y, Ng HH, Erdjument-Bromage H, Tempst P, Bird A, Reinberg D (1999) Analysis of the NuRD subunits reveals a histone deacetylase core complex and a connection with DNA methylation. Genes Dev 13:1924–1935PubMedCrossRef Zhang Y, Ng HH, Erdjument-Bromage H, Tempst P, Bird A, Reinberg D (1999) Analysis of the NuRD subunits reveals a histone deacetylase core complex and a connection with DNA methylation. Genes Dev 13:1924–1935PubMedCrossRef
25.
Zurück zum Zitat Xia L, Zhang Y (2001) Sp1 and ETS family transcription factors regulate the mouse Mta2 gene expression. Gene 268:77–85PubMedCrossRef Xia L, Zhang Y (2001) Sp1 and ETS family transcription factors regulate the mouse Mta2 gene expression. Gene 268:77–85PubMedCrossRef
Metadaten
Titel
Expression of metastasis-associated protein 2 (MTA2) might predict proliferation in non-small cell lung cancer
verfasst von
Shu-Li Liu
Yang Han
Yong Zhang
Cheng-Yao Xie
En-Hua Wang
Yuan Miao
Hai-Ying Li
Hong-Tao Xu
Shun-Dong Dai
Publikationsdatum
01.06.2012
Verlag
Springer-Verlag
Erschienen in
Targeted Oncology / Ausgabe 2/2012
Print ISSN: 1776-2596
Elektronische ISSN: 1776-260X
DOI
https://doi.org/10.1007/s11523-012-0215-z

Weitere Artikel der Ausgabe 2/2012

Targeted Oncology 2/2012 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.