Transcriptional changes in U343 MG-a glioblastoma cell line exposed to ionizing radiation

Abstract

<jats:p> Glioblastoma multiforme (GBM) is a highly invasive and radioresistant brain tumor. Aiming to study how glioma cells respond to γ-rays in terms of biological processes involved in cellular responses, we performed experiments at cellular context and gene expression analysis in U343-MG-a GBM cells irradiated with 1 Gy and collected at 6 h post-irradiation. The survival rate was approximately 61% for 1 Gy and was completely reduced at 16 Gy. By performing the microarray technique, 859 cDNA clones were analyzed. The Significance Analysis of Microarray algorithm indicated 196 significant expressed genes (false discovery rate (FDR) = 0.42%): 67 down-regulated and 97 up-regulated genes, which belong to several classes: metabolism, adhesion/cytoskeleton, signal transduction, cell cycle/apoptosis, membrane transport, DNA repair/DNA damage signaling, transcription factor, intracellular signaling, and RNA processing. Differential expression patterns of five selected genes ( HSPA9B, INPP5A, PIP5K1A, FANCG, and TPP2) observed by the microarray analysis were further confirmed by the quantitative real time RT-PCR method, which demonstrated an up-regulation status of those genes. These results indicate a broad spectrum of biological processes (which may reflect the radio-resistance of U343 cells) that were altered in irradiated glioma cells, so as to guarantee cell survival. </jats:p>

Relationship of differential gene expression profiles in CD34+ myelodysplastic syndrome marrow cells to disease subtype and progression

“…34,35 TPP2 is a protease involved in intracellular proteolysis that is upregulated in irradiated glioblastoma cells, enhancing tumor cell survival and radio-resistance. 36 Confirmation of the relative levels of increased gene expression of specific genes, including those in the poor risk signature assessed by microarray was demonstrated using PCR analysis. Noteworthy are the relatively differing expression levels of relevant genes between tMDS and sMDS patients, as shown by the 2 independent methods.…”

Chronic stress and impaired glutamate function elicit a depressive-like phenotype and common changes in gene expression in the mouse frontal cortex

“…either structural changes such as an increased neuronal death, neurite atrophia or molecular changes that lead to a failure in synaptic function and plasticity (Duman et al, 2006) b On the other hand, perhaps as compensatory mechanims, genes supposed to be neuroprotective such as an inhibitor of apoptosis (Pip5k1a; phosphatidylinositol4phosphate 5-kinase, type 1 alpha), (Bassi et al, 2008) …”

Efeitos do Silenciamento de E2F1 e HEB, Fatores de Transcrição Preditos In Silico, em Células de Glioblastoma Irradiadas com Raios Gama.

“…This approach allows comparisons between different biological situations . In a previous work, several stress response/DNA repair genes, such as HSPA9B, INPP5A, PIP5K1A, FANCG, and TPP2 were found up-regulated in U343MG-a GBM cells analyzed at 6 h following irradiation with 1 Gy, reflecting the radio-resistance of these cells; at this condition, the survival rate was 61%, and a broad spectrum of other biological processes was found associated to the list of differentially expressed genes in irradiated cells (Bassi et al, 2008). TP53 gene plays a role in drug and radioresistance mechanisms, but the complex network of signaling pathways involving this gene is not well elucidated.…”

“…In the present work, we studied four GBM cell lines with different TP53 status; T98G and U251MG are mutated and U343MG-a and U87MG are wild-type for TP53 gene, but they are similar regarding the fact that they harbor mutations for CDKN2A and PTEN, according to Ishi et al (1999). In experiments on cell survival performed by the clonogenic survival assay, the results provided by several authors indicated that MT TP53 cells were, in general, more radioresistant than WT TP53 cells (Bassi et al, 2008;Chautard et al, 2010;de la Pena et al, 2006;Lee et al, 2006;Roy et al, 2006). As described above, several differentially expressed genes provided by the comparison between MT versus WT TP53 GBM cells are involved in the mechanism of resistance to ionizing radiation and/or multidrug resistance.…”