Abstract
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 intrachromosoreal 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 reexpressed in gliomas and may become a key target of intrachromosomal amplification upon 19q rearrangements.
| Original language | English |
|---|---|
| Pages (from-to) | 2581-2591 |
| Number of pages | 11 |
| Journal | Oncogene |
| Volume | 22 |
| Issue number | 17 |
| Publication status | Published - May 1 2003 |
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Keywords
- Glioma
- Intrachromosomal amplification
- MARK4
- Neural progenitor
- Upregulation and overexpression
- Wnt pathway
ASJC Scopus subject areas
- Molecular Biology
- Cancer Research
- Genetics
Cite this
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. / Beghini, Alessandro; Magnani, Ivana; Roversi, Gaia; Piepoli, Tiziana; Di Terlizzi, Simona; Moroni, Ramona F.; Pollo, Bianca; Fuhrman Conti, Anna M.; Cowell, John K.; Finocchiaro, Gaetano; Larizza, Lidia.
In: Oncogene, Vol. 22, No. 17, 01.05.2003, p. 2581-2591.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - 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
AU - Beghini, Alessandro
AU - Magnani, Ivana
AU - Roversi, Gaia
AU - Piepoli, Tiziana
AU - Di Terlizzi, Simona
AU - Moroni, Ramona F.
AU - Pollo, Bianca
AU - Fuhrman Conti, Anna M.
AU - Cowell, John K.
AU - Finocchiaro, Gaetano
AU - Larizza, Lidia
PY - 2003/5/1
Y1 - 2003/5/1
N2 - 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 intrachromosoreal 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 reexpressed in gliomas and may become a key target of intrachromosomal amplification upon 19q rearrangements.
AB - 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 intrachromosoreal 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 reexpressed in gliomas and may become a key target of intrachromosomal amplification upon 19q rearrangements.
KW - Glioma
KW - Intrachromosomal amplification
KW - MARK4
KW - Neural progenitor
KW - Upregulation and overexpression
KW - Wnt pathway
UR - http://www.scopus.com/inward/record.url?scp=0038530985&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0038530985&partnerID=8YFLogxK
M3 - Article
C2 - 12735302
AN - SCOPUS:0038530985
VL - 22
SP - 2581
EP - 2591
JO - Oncogene
JF - Oncogene
SN - 0950-9232
IS - 17
ER -