Portrait of Transcriptional Expression Profiles Displayed by Different Glioblastoma Cell Lines

Godoy, Paulo R. D. V.; Mello, Stephano S.; Magalhães, Daniele A.; Donaires, Flávia S.; Lima-Montaldi, Ana P.; Nicolucci, Patrícia; Donadi, Eduardo Antônio; Passos, Geraldo Aleixo Silva; Sakamoto-Hojo, Elza Tiemi

doi:10.5772/22322

Cited by 4 publications

(7 citation statements)

References 74 publications

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“…Therefore, cadherins are considered as potential targets to reduce chemo-and radioresistance (40). Our previous study revealed an upregulation of three cadherins (CDH8, CDH13 and CD93) and one integrin (ITGA5) in mutated TP53 GBM cell lines compared with wild-type cells (6).…”

Section: Discussionmentioning

confidence: 98%

“…Cells were then analyzed for cell death, proliferation and cell cycle kinetics (at 24, 48 and 72 h following irradiation). To assess the efficiency of transfection, 1x10 6 cells were seeded and harvested after 72 h for western blotting. The scrambled sequence (SCR; catalog no.…”

Section: Methodsmentioning

confidence: 99%

“…Among the high mutational background, mutations in TP53 have been detected in 31% of cases of primary GBM (4). TP53 status affects transcriptional profiles in tumor cell lines (5,6), including GBM cells exposed to irradiation (7,8).…”

Section: Introductionmentioning

confidence: 99%

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HEB silencing induces anti-proliferative effects on U87MG cells cultured as neurospheres and monolayers

Godoy

Montaldi

Sakamoto-Hojo

2016

Molecular Medicine Reports

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Glioblastoma multiforme (GBM) is a lethal tumor and novel strategies are required to overcome resistance. Transcription factor 12 (HEB) has been associated with neural and stem cell proliferation, is overexpressed in certain tumor types and is induced in irradiated U87MG cells. The present study aimed to determine whether HEB knockdown, with or without irradiation, may sensitize GBM cells. U87MG GBM and ACBRI‑371 primary human astrocytes were cultured in monolayers or neurospheres. Cell proliferation and death, cell cycle and sub‑G1 detection, and cluster of differentiation (CD) 133 immunofluorescence were analyzed by flow cytometry, whereas HEB protein expression was analyzed by immunocytochemistry and western blotting. Greater HEB protein expression was observed in U87MG neurospheres compared with ACBRI‑371, and the two cell lines exhibited nuclear HEB expression. HEB silencing in cells grown in monolayers induced a significant reduction in proliferation and decreased the proportion of cells in G0/G1 phase. In addition, HEB silencing reduced (two‑fold) the number of neurospheres compared with control scrambled (SCR) cells. HEB silencing combined with irradiation reduced U87MG cell proliferation when cultured in monolayers and reduced neurosphere cell number compared with the SCR irradiated group; however, not significantly. Differentiation of U87MG cells from neurospheres was reduced in HEB‑silenced cells, whereas in irradiated cells the proportion of CD133+ cells was similar in HEB‑silenced cells compared with the SCR control. These results suggest that HEB may contribute to the proliferation and maintenance of GBM cells. However, only limited effects were exerted by irradiation in HEB‑silenced cells. HEB may be a potential target to decrease proliferation in U87MG GBM cells, grown as monolayers or neurospheres, and may provide important information for the development of novel strategies for cancer therapy.

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Section: Discussionmentioning

confidence: 98%

Section: Methodsmentioning

confidence: 99%

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HEB silencing induces anti-proliferative effects on U87MG cells cultured as neurospheres and monolayers

Godoy

Montaldi

Sakamoto-Hojo

2016

Molecular Medicine Reports

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“…Hybridizations were carried out using an automatic system (Automatic Slide Processor, Amersham Biosciences, UK) and signals were immediately captured after the final wash procedure, using a Generation III laser scanner (Amersham Biosciences, UK). This array platform was already used in several studies [22][23][24][25][26]36].…”

Section: Cdna Microarrays Methods and Analysismentioning

confidence: 99%

“…A valuable tool to study the transcription machinery is the DNA microarray technology [19], which measures the transcript expression of thousands of genes to identify changes in expression profiles at different biological conditions [20][21][22][23][24], thus allowing to compare different cell types under diverse treatment conditions. The influence of TP53 status on transcriptional profiles was previously described in tumor cell lines [25,26]. Expression signatures of irradiated GBM cells were already performed for cell lines that are proficient and deficient for TP53 [27,28].…”

Section: Introductionmentioning

confidence: 99%

In silico Analysis of Transcription Factors Associated to Differentially Expressed Genes in Irradiated Glioblastoma Cell Lines

Godoy¹,

Mello²,

Donaires³

et al. 2013

Evolution of the Molecular Biology of Brain Tumors and the Therapeutic Implications

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Anti-Proliferative Effects of E2F1 Suppression in Glioblastoma Cells

Godoy

Donaires

Montaldi

et al. 2021

Cytogenet Genome Res

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Glioblastoma (GBM) is an aggressive malignant brain tumor; surgery, radiation, and temozolomide still remain the main treatments. There is evidence that E2F1 is overexpressed in various types of cancer, including GBM. E2F1 is a transcription factor that controls the cell cycle progression and regulates DNA damage responses and the proliferation of pluripotent and neural stem cells. To test the potentiality of E2F1 as molecular target for GBM treatment, we suppressed the <i>E2F1</i> gene (siRNA) in the U87MG cell line, aiming to inhibit cellular proliferation and modulate the radioresistance of these cells. Following E2F1 suppression, associated or not with gamma-irradiation, several assays (cell proliferation, cell cycle analysis, neurosphere counting, and protein expression) were performed in U87MG cells grown as monolayer or neurospheres. We found that siE2F1-suppressed cells showed reduced cell proliferation and increased cell death (sub-G1 fraction) in monolayer cultures, and also a significant reduction in the number of neurospheres. In addition, in irradiated cells, E2F1 suppression caused similar effects, with reduction of the number of neurospheres and neurosphere cell numbers relative to controls; these results suggest that E2F1 plays a role in the maintenance of GBM stem cells, and our results obtained in neurospheres are relevant within the context of radiation resistance. Furthermore, E2F1 suppression inhibited or delayed GBM cell differentiation by maintaining a reasonable proportion of CD133+ cells when grown at differentiation condition. Therefore, E2F1 proved to be an interesting molecular target for therapeutic intervention in U87MG cells.

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Portrait of Transcriptional Expression Profiles Displayed by Different Glioblastoma Cell Lines

Cited by 4 publications

References 74 publications

HEB silencing induces anti-proliferative effects on U87MG cells cultured as neurospheres and monolayers

HEB silencing induces anti-proliferative effects on U87MG cells cultured as neurospheres and monolayers

In silico Analysis of Transcription Factors Associated to Differentially Expressed Genes in Irradiated Glioblastoma Cell Lines

Anti-Proliferative Effects of E2F1 Suppression in Glioblastoma Cells

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