Minichromosome maintenance (MCM) protein 4 as a marker for proliferation and its clinical and clinicopathological significance in non-small cell lung cancer

Abstract Background Minichromosome maintenance (MCM) proteins 2–7 form a complex essential for the initiation of DNA replication. In the process to screen expression changes related to growth suppression of non-small cell lung cancer (NSCLC) cells by a cJun dominant-negative mutant, we found that re...

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Published in:Lung cancer (Amsterdam, Netherlands) Netherlands), 2011-05, Vol.72 (2), p.229-237
Main Authors: Kikuchi, Junko, Kinoshita, Ichiro, Shimizu, Yasushi, Kikuchi, Eiki, Takeda, Kayoko, Aburatani, Hiroyuki, Oizumi, Satoshi, Konishi, Jun, Kaga, Kichizo, Matsuno, Yoshihiro, Birrer, Michael J, Nishimura, Masaharu, Dosaka-Akita, Hirotoshi
Format: Article
Language:English
Subjects:
Aged
AP-1
Biological and medical sciences
Biomarkers, Tumor - genetics
Biomarkers, Tumor - metabolism
Carcinoma, Non-Small-Cell Lung - genetics
Carcinoma, Non-Small-Cell Lung - metabolism
Carcinoma, Non-Small-Cell Lung - mortality
Carcinoma, Non-Small-Cell Lung - pathology
Carcinoma, Non-Small-Cell Lung - physiopathology
Cell Cycle Proteins - genetics
Cell Cycle Proteins - metabolism
Cell Growth Processes - genetics
Cell Line, Tumor
Cyclin E - genetics
Cyclin E - metabolism
DNA-Binding Proteins - genetics
DNA-Binding Proteins - metabolism
Female
Hematology, Oncology and Palliative Medicine
Humans
Immunohistochemistry
JNK Mitogen-Activated Protein Kinases - genetics
Ki-67 Antigen - genetics
Ki-67 Antigen - metabolism
Lung Neoplasms - genetics
Lung Neoplasms - metabolism
Lung Neoplasms - mortality
Lung Neoplasms - pathology
Lung Neoplasms - physiopathology
Male
Medical sciences
Minichromosome Maintenance Complex Component 4
Minichromosome maintenance protein 4
Mutation - genetics
Non-small cell lung cancer
Nuclear Proteins - genetics
Nuclear Proteins - metabolism
Pneumology
Proliferation
Pulmonary/Respiratory
Respiratory Mucosa - metabolism
Respiratory Mucosa - pathology
RNA, Small Interfering - genetics
Sex Factors
Survival Analysis
TAM67
Tumors
Tumors of the respiratory system and mediastinum
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Summary:Abstract Background Minichromosome maintenance (MCM) proteins 2–7 form a complex essential for the initiation of DNA replication. In the process to screen expression changes related to growth suppression of non-small cell lung cancer (NSCLC) cells by a cJun dominant-negative mutant, we found that reduced expression of MCM4 was correlated with this growth suppression. Method We determined the relevance of MCM4 in proliferation of NSCLC by downregulating its expression with small-interfering RNA in three NSCLC cell lines. We then immunohistochemically analyzed MCM4 expression in 156 surgically resected NSCLCs to correlate clinicopathologic characteristics. Results MCM4 downregulation reduced proliferation in two cell lines. MCM4 expression was higher in cancer cells than in adjacent normal bronchial epithelial cells ( p < 0.001). High MCM4 expression was correlated with male gender, heavy smoking, poorer differentiation and non-adenocarcinoma histology ( p < 0.001, respectively). High MCM4 expression was also correlated with proliferation markers, Ki-67 and cyclin E expression ( p < 0.001, respectively). MCM4 expression was not associated with survival. Conclusion MCM4 may play an essential role in the proliferation of some NSCLC cells. Taken together with higher expression in NSCLCs and its correlation with clinicopathologic characteristics such as non-adenocarcinoma histology, MCM4 may have potential as a therapeutic target in certain population with NSCLCs.
ISSN:0169-5002
1872-8332
DOI:10.1016/j.lungcan.2010.08.020