Abstract
BackgroundThe 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.ResultsImmunohistochemical 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.ConclusionsSince 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.
Highlights
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
Minichromosome Maintenance Protein 7 (MCM7) expression is significantly high in lung cancer tissues and correlated with poor prognosis in non-small cell lung cancer (NSCLC) We previously reported that PRMT6, a type I arginine methytransferase, is involved in human carcinogenesis [27]
We analyzed the association of MCM7 expression with clinical outcomes, and found that expression of MCM7 in NSCLC patients was significantly associated with male gender (P < 0.0001, Fisher’s exact test; Table 1), non-adenocarcinoma (ADC) histology (P < 0.0001), presence of lymph node metastasis and tumor-specific 5-year survival after the resection of primary tumors (P = 0.0055 by log-rank test; Figure 1D)
Summary
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. Even in patients with advanced solid tumors or recurrences following surgery, chemotherapy can offer lengthened survival of worthwhile quality In those patients, the therapeutic index is narrow: responses are usually partial, often disappointingly brief. MCM proteins are essential replication initiation and elongation factors originally found in Saccharomyces cerevisiae, existing in a functional complex consisting of MCM2-7. They are evolutionarily conserved in all eukaryotes [9]. It is known that aberrant DNA replication leads to pathological disorders including cancer, how dysregulated MCM proteins contribute to carcinogenesis, and aggressive cancer with poor prognosis, is unclear
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