title: Depletion of minichromosome maintenance protein 7 inhibits glioblastoma multiforme tumor growth in vivo.
abstract: Minichromosome maintenance (MCM) proteins are key elements that function as a part of the pre-replication complex to initiate DNA replication in eukaryotes. Consistent with their roles in initiating DNA replication, overexpression of MCM family members has been observed in several malignancies. Through bioinformatic analysis of The Cancer Genome Atlas's data on glioblastoma multiforme (GBM), we found that the genomic region containing MCM7 gene was amplified in more than 80% of the present cases. To validate this finding and to identify the possible contribution of the remaining members of the MCM family to GBM progression, we used quantitative real-time PCR to analyze the gene expression profiles of all MCM family members in Grade IV (GBM) tissue samples and observed a significant upregulation in GBM samples compared with normal white matter tissues. In addition, we compared the observed gene expression profiles with those of Grade II and Grade III astrocytoma samples and determined that the observed upregulation was restricted and specific to Grade IV. MCM7 was the most upregulated gene in the gene set we analyzed, and therefore we wanted to identify the role of MCM7 in GBM progression. We determined that siRNA-mediated knockdown of MCM7 expression reduced GBM cell proliferation and also inhibited tumor growth in both xenograft and orthotopic mouse models of GBM. Taken together, our data suggest that MCM7 can be a potential prognostic marker and a novel therapeutic target in GBM therapy.
authors.affiliation: Molecular Neuro-Oncology Research Unit, Department of Pediatrics, Medical University of Vienna, Vienna, Austria.
authors.forename: E P
authors.initials: EP
authors.lastname: Erkan
authors.affiliation: Institute of Neurology, Medical University of Vienna, Vienna, Austria.
authors.forename: T
authors.initials: T
authors.lastname: Ströbel
authors.affiliation: Experimental Therapeutics and Molecular Imaging Laboratory, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: G
authors.initials: G
authors.lastname: Lewandrowski
authors.affiliation: Experimental Therapeutics and Molecular Imaging Laboratory, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: B
authors.initials: B
authors.lastname: Tannous
authors.affiliation: Molecular Neuro-Oncology Research Unit, Department of Pediatrics, Medical University of Vienna, Vienna, Austria.
authors.forename: S
authors.initials: S
authors.lastname: Madlener
authors.affiliation: Department of Neurosurgery, Medical University of Vienna, Vienna, Austria.
authors.forename: T
authors.initials: T
authors.lastname: Czech
authors.affiliation: Molecular Neuro-Oncology Research Unit, Department of Pediatrics, Medical University of Vienna, Vienna, Austria.
authors.forename: N
authors.initials: N
authors.lastname: Saydam
authors.affiliation: Molecular Neuro-Oncology Research Unit, Department of Pediatrics, Medical University of Vienna, Vienna, Austria.
authors.forename: O
authors.initials: O
authors.lastname: Saydam
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D005909:Glioblastoma / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D064168:Minichromosome Maintenance Complex Component 7 / Q000235:genetics* / Q000378:metabolism; D009368:Neoplasm Transplantation; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D047368:Tumor Burden
chemical_list: D012333:RNA, Messenger; D034741:RNA, Small Interfering; C101624:MCM7 protein, human; D064168:Minichromosome Maintenance Complex Component 7