Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2008-1-21
pubmed:abstractText
Emerging evidence suggests that neural stem cells and brain tumors regulate their proliferation via similar pathways. In a previous study, we demonstrated that maternal embryonic leucine zipper kinase (Melk) is highly expressed in murine neural stem cells and regulates their proliferation. Here we describe how MELK expression is correlated with pathologic grade of brain tumors, and its expression levels are significantly correlated with shorter survival, particularly in younger glioblastoma patients. In normal human astrocytes, MELK is only faintly expressed, and MELK knockdown does not significantly influence their growth, whereas Ras and Akt overexpressing astrocytes have up-regulated MELK expression, and the effect of MELK knockdown is more prominent in these transformed astrocytes. In primary cultures from human glioblastoma and medulloblastoma, MELK knockdown by siRNA results in inhibition of the proliferation and survival of these tumors. Furthermore, we show that MELK siRNA dramatically inhibits proliferation and, to some extent, survival of stem cells isolated from glioblastoma in vitro. These results demonstrate a critical role for MELK in the proliferation of brain tumors, including their stem cells, and suggest that MELK may be a compelling molecular target for treatment of high-grade brain tumors.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0360-4012
pubmed:author
pubmed:issnType
Print
pubmed:volume
86
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
48-60
pubmed:meshHeading
pubmed-meshheading:17722061-Adult, pubmed-meshheading:17722061-Aged, pubmed-meshheading:17722061-Animals, pubmed-meshheading:17722061-Brain Neoplasms, pubmed-meshheading:17722061-Cell Proliferation, pubmed-meshheading:17722061-Cells, Cultured, pubmed-meshheading:17722061-Female, pubmed-meshheading:17722061-Flow Cytometry, pubmed-meshheading:17722061-Gene Expression Regulation, Neoplastic, pubmed-meshheading:17722061-Glioblastoma, pubmed-meshheading:17722061-Humans, pubmed-meshheading:17722061-Male, pubmed-meshheading:17722061-Mass Spectrometry, pubmed-meshheading:17722061-Mice, pubmed-meshheading:17722061-Mice, Knockout, pubmed-meshheading:17722061-Middle Aged, pubmed-meshheading:17722061-Neoplastic Stem Cells, pubmed-meshheading:17722061-Pituitary Adenylate Cyclase-Activating Polypeptide, pubmed-meshheading:17722061-Protein-Serine-Threonine Kinases, pubmed-meshheading:17722061-RNA, Small Interfering, pubmed-meshheading:17722061-Receptors, Cell Surface, pubmed-meshheading:17722061-Transfection
pubmed:year
2008
pubmed:articleTitle
Maternal embryonic leucine zipper kinase is a key regulator of the proliferation of malignant brain tumors, including brain tumor stem cells.
pubmed:affiliation
Department of Neurosurgery, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural