Transcriptional Characterization of Glioma Neural Stem Cells Diva ...

7.3 Tumour Expression Correlation Results
of the dot indicates the direction (red or blue) and the magnitude (intensity
of red or blue) of the FC as measured via qRT-PCR and in doing so adopts
the same colour scheme of the heatmap in 7.4. Table 7.4 summarises all the
information gathered in the literature searches for the 29 genes differentially
expressed as measured via qRT-PCR, information that is expanded upon in
the paragraphs below.
Up-regulated in GNS cell lines. The genes HOXD10, CD9, PLA2G4A,
MT2A, SULF2, DDIT3, PLS3, CEBPB, PRSS12 and LYST are all highly ex-
pressed in both GNS cell lines and primary GBMs. On the contrary, genes
FOXG1, LMO4, ADD2 and PDE1C are up-regulated in GNS cell lines but are
down-regulated in primary GBMs.
Interestingly, FOXG1 is proposed to act as an oncogene in GBM by suppress-
ing the growth inhibitory effects of TGFβ [448], so that the up-regulation we
observe in GNS cell lines (Fig 7.4a) could be a cell type specific regulation that
especially affects the stem cell component of the tumour. This would corrob-
orate the hypothesis that NS cells are candidates for tumour-initiating cells
in GBM. Also this up-regulation is not mirrored in grade III astrocytomas,
indicating different oncogenic factors in action (Fig 7.4b).
The transcriptional regulator LMO4 is of particular interest as it is involved in
the development of multiple organs, including the CNS, and its expression is
elevated in several cancers [202,339,475,488,542]. LMO4 is especially well stud-
ied as an oncogene in breast cancer and regulated through the phosphoinosi-
tide 3-kinase pathway [340], which is commonly affected in glioblastoma [326].
Similarly to FOXG1, the up-regulation of LMO4 in GNS cell lines but not
in primary GBM (Fig 7.4a) could be reflective of its oncogenic role in GBM
tumour-initiating cells. Interestingly, LMO4 could be an oncogene early at
work in the progression of the disease from a lower to a higher grade, as its
up-regulation is observed in grade III astrocytomas (Fig 7.4b).
The ADD2 gene encodes a cytoskeletal protein that interacts with FYN, a
tyrosine kinase promoting cancer cell migration [456,533]. The up-regulation
of this gene in GNS cell lines is reflective of the invasiveness that charac-
terises GBM, and is possibly lost through differentiation since ADD2 appears
to be down-regulated in primary GBM data (Fig 7.4a). The small level of
up-regulation observed for this gene in grade III astrocytomas (Fig 7.4b) is a
reflection of its activity early on in the progression of the disease.
PDE1C is a cyclic nucleotide phosphodiesterase gene that we observe to be up-
regulated in GNS cell lines and down-regulated in primary GBM (Fig 7.4a).
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