MCM7 amplification and overexpression are associated with prostate cancer progression.
The genomic DNA profiles of prostate cancers with aggressive features were compared to the profiles of matched normal DNA to identify genes that are selectively amplified in the cancer cells. One of the identified genes, MCM7, which is a component of the DNA replication licensing complex, has been studied extensively both at the DNA and protein levels in human prostate tissues. Approximately half of the prostate cancer specimens studied showed MCM7 gene amplification, and 60% of the aggressive prostate cancer specimens had increased MCM7 protein expression. Amplification or overexpression of MCM7 was significantly associated with relapse, local invasion and a worse tumor grade. Constitutive expression of MCM7 in a human prostate cancer cell line, DU145, resulted in markedly increased DNA synthesis and cell proliferation compared to vector-only controls, and an increased cell invasion in vitro. Indeed, MCM7 overexpression produced primary tumors 12 times larger than vector-only controls and resulted in a rapid demise of mice bearing those tumors. These studies implicate MCM7, and the DNA replication licensing gene family, in prostate cancer progression, growth and invasion.
Ren
B
B
Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
Yu
G
G
Tseng
G C
GC
Cieply
K
K
Gavel
T
T
Nelson
J
J
Michalopoulos
G
G
Yu
Y P
YP
Luo
J-H
JH
D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D018450:Disease Progression; D005784:Gene Amplification; D018628:Gene Dosage; D006801:Humans; D008297:Male; D051379:Mice; D016513:Mice, SCID; D064168:Minichromosome Maintenance Complex Component 7; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology*
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C101624:MCM7 protein, human; D064168:Minichromosome Maintenance Complex Component 7