The neural progenitor-restricted isoform of the MARK4 gene in 19q13.2 is upregulated in human gliomas and overexpressed in a subset of glioblastoma cell lines.
Alterations of 19q13 are frequently observed in glial neoplasms, suggesting that this region harbors at least one gene involved in gliomagenesis. Following our previous studies on structural 19q chromosome rearrangements in gliomas, we have undertaken a detailed FISH analysis of the breakpoints and identified a 19q13.2 intrachromosomal amplification of the MAP/microtubule affinity-regulating kinase 4 (MARK4) gene in three primary glioblastoma cell lines. Recent data suggest that this gene is involved in the Wnt-signaling pathway. We observed that the expression of the alternatively spliced MARK4L isoform is upregulated in both fresh and cultured gliomas and overexpressed in all of the above three glioblastoma cell lines. Interestingly, we also found that MARK4L expression is restricted to undifferentiated neural progenitor cells or proliferating glial precursor cells, whereas its expression is downregulated during glial differentiation. Perturbation of expression using antisense oligonucleotides against MARK4 in glioblastoma cell lines, consistently induced a decreased proliferation of tumor cells. Taken together, these data show that MARK4, which is normally expressed in neural progenitors, is re-expressed in gliomas and may become a key target of intrachromosomal amplification upon 19q rearrangements.
Beghini
Alessandro
A
Department of Biology and Genetics, University of Milan, via Viotti 3/5, 20133 Milan, Italy. alessandro.beghini@unimi.it
Magnani
Ivana
I
Roversi
Gaia
G
Piepoli
Tiziana
T
Di Terlizzi
Simona
S
Moroni
Ramona F
RF
Pollo
Bianca
B
Fuhrman Conti
Anna M
AM
Cowell
John K
JK
Finocchiaro
Gaetano
G
Larizza
Lidia
L
D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002888:Chromosomes, Human, Pair 19; D005909:Glioblastoma / Q000378:metabolism*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008969:Molecular Sequence Data; D009457:Neuroglia / Q000502:physiology; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D017384:Sequence Deletion; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D020033:Protein Isoforms; D017346:Protein Serine-Threonine Kinases