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Minichromosome Maintenance Protein 7 is a potential therapeutic target in human cancer and a novel prognostic marker of non-small cell lung cancer.


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Authors

Toyokawa, Gouji 
Masuda, Ken 
Daigo, Yataro 
Cho, Hyun-Soo 
Yoshimatsu, Masanori 

Abstract

BACKGROUND: The research emphasis in anti-cancer drug discovery has always been to search for a drug with the greatest antitumor potential but fewest side effects. This can only be achieved if the drug used is against a specific target located in the tumor cells. In this study, we evaluated Minichromosome Maintenance Protein 7 (MCM7) as a novel therapeutic target in cancer. RESULTS: Immunohistochemical analysis showed that MCM7 was positively stained in 196 of 331 non-small cell lung cancer (NSCLC), 21 of 29 bladder tumor and 25 of 70 liver tumor cases whereas no significant staining was observed in various normal tissues. We also found an elevated expression of MCM7 to be associated with poor prognosis for patients with NSCLC (P = 0.0055). qRT-PCR revealed a higher expression of MCM7 in clinical bladder cancer tissues than in corresponding non-neoplastic tissues (P < 0.0001), and we confirmed that a wide range of cancers also overexpressed MCM7 by cDNA microarray analysis. Suppression of MCM7 using specific siRNAs inhibited incorporation of BrdU in lung and bladder cancer cells overexpressing MCM7, and suppressed the growth of those cells more efficiently than that of normal cell strains expressing lower levels of MCM7. CONCLUSIONS: Since MCM7 expression was generally low in a number of normal tissues we examined, MCM7 has the characteristics of an ideal candidate for molecular targeted cancer therapy in various tumors and also as a good prognostic biomarker for NSCLC patients.

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Keywords

Biomarkers, Tumor, Carcinoma, Non-Small-Cell Lung, Cell Cycle Proteins, Cell Line, Tumor, Cell Proliferation, DNA-Binding Proteins, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Gene Silencing, HCT116 Cells, HEK293 Cells, HeLa Cells, Hep G2 Cells, Humans, Lung Neoplasms, Minichromosome Maintenance Complex Component 7, Neoplasms, Nuclear Proteins, Prognosis, Protein Binding, Protein-Arginine N-Methyltransferases, RNA, Small Interfering

Journal Title

Mol Cancer

Conference Name

Journal ISSN

1476-4598
1476-4598

Volume Title

Publisher

Springer Science and Business Media LLC