<i>PIK3CA</i> Gene Mutations in Pediatric and Adult Glioblastoma Multiforme

Gallia, Gary L.; Rand, Vikki; Siu, I-Mei; Eberhart, Charles G.; James, C. David; Marie, Suely Kazue Nagahashi; Oba-Shinjo, Sueli Mieko; Carlotti, Carlos Gilberto; Caballero, Otávia L.; Simpson, Andrew J.G.; Brock, Malcolm V.; Massion, Pierre P.; Carson, Benjamin S.; Riggins, Gregory J.

doi:10.1158/1541-7786.mcr-06-0172

Cited by 152 publications

(113 citation statements)

References 26 publications

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“…PI3K regulates the single transmission of AKT phosphorylation. (Gallia et al, 2006, Kita et al, 2007 Several studies show that PI3K inhibition sensitizes glioma cells to radiation and chemical therapy (Opel et al, 2008;Prevo et al, 2008). Modulation of AKT signalling cascade using miRNAs in glioblastoma cell lines was described also in Nan et al In this study, transfection of miR-451 mimicked reduced expression levels of Akt1, Cyclin D1, MMP-2, MMP-9 and Bcl-2.…”

Section: Discussionsupporting

confidence: 59%

MicroRNA-451 Inhibits Growth of Human Colorectal Carcinoma Cells via Downregulation of Pi3k/Akt Pathway

Zhang²,

Cai³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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MicroRNAs (MiRNAs) play important roles in coordinating a variety of cellular processes and abnormal expression has been linked to the occurrence of several cancers. The miRNA miR-451 is downregulated in colorectal carcinoma (CRC) cells, suggested by several research groups including our own. In this study, synthetic miR-451 mimics were transfected into the SW620 human CRC cell line using Lipofectamine 2000 and expression of miR-451 was analyzed by real time PCR, while expression of CAB39, LKB1, AMPK, AKT, PI3K and Bcl2 was analyzed by Western blot, and cell growth was detected by MTT assay. In comparison to the controls, a significant increase in the expression of miR-451 was associated with significantly decreased expression of CAB39, LKB1, AMPK, AKT, PI3K and Bcl2. The capacity of cell proliferation was significantly decreased by miR-451 expression, which also inhibited cell growth. Our study confirmed that miR-451 has a repressive role in CRC cells by inhibiting cell growth through down-regulating the P13K/AKT pathway.

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Section: Discussionsupporting

confidence: 59%

MicroRNA-451 Inhibits Growth of Human Colorectal Carcinoma Cells via Downregulation of Pi3k/Akt Pathway

Zhang²,

Cai³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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“…This pathway also promotes tumor survival after radiation-induced DNA damage [12] . Dysregulation of this pathway is frequently observed in GBM and occurs via multiple mechanisms, including mutation of the PIK3CA gene [13] , deregulation of mTOR complexes [14] , and loss or mutation of the phosphatase and tensin homolog [15] . Inhibition of this cascade can enhance radiosensitivity of the tumor cells without affecting the normal cells, which is an attractive concept for improving therapeutic outcomes [16] .…”

Section: Introductionmentioning

confidence: 99%

NVP-BEZ235, a novel dual PI3K/mTOR inhibitor, enhances the radiosensitivity of human glioma stem cells in vitro

et al. 2013

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Aim: NVP-BEZ235 is a novel dual PI3K/mTOR inhibitor and shows dramatic effects on gliomas. The aim of this study was to investigate the effects of NVP-BEZ235 on the radiosensitivity and autophagy of glioma stem cells (GSCs) in vitro. Methods: Human GSCs (SU-2) were tested. The cell viability and survival from ionizing radiation (IR) were evaluated using MTT and clonogenic survival assay, respectively. Immunofluorescence assays were used to identify the formation of autophagosomes. The apoptotic cells were quantified with annexin V-FITC/PI staining and flow cytometry, and observed using Hoechst 33258 staining and fluorescence microscope. Western blot analysis was used to analyze the expression levels of proteins. Cell cycle status was determined by measuring DNA content after staining with PI. DNA repair in the cells was assessed using a comet assay. Results: Treatment of SU-2 cells with NVP-BEZ235 (10-320 nmol/L) alone suppressed the cell growth in a concentration-dependent manner. A low concentration of NVP-BEZ235 (10 nmol/L) significantly increased the radiation sensitivity of SU-2 cells, which could be blocked by co-treatment with 3-MA (50 µmol/L). In NVP-BEZ235-treated SU-2 cells, more punctate patterns of microtubule-associated protein LC3 immunoreactivity was observed, and the level of membrane-bound LC3-II was significantly increased. A combination of IR with NVP-BEZ235 significantly increased the apoptosis of SU-2 cells, as shown in the increased levels of BID, Bax, and active caspase-3, and decreased level of Bcl-2. Furthermore, the combination of IR with NVP-BEZ235 led to G 1 cell cycle arrest. Moreover, NVP-BEZ235 significantly attenuated the repair of IR-induced DNA damage as reflected by the tail length of the comet. Conclusion: NVP-BEZ235 increases the radiosensitivity of GSCs in vitro by activating autophagy that is associated with synergistic increase of apoptosis and cell-cycle arrest and decrease of DNA repair capacity.

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“…Elevated AKT phosphorylation has been observed in up to 85% of glioblastoma cell lines and patient samples [45]. RTK-independent activation of this pathway in glioblastoma can occur via mutation or amplification of PIK3CA (p110a) [46,47], and PIK3CD (p110d) is also overexpressed in some gliomas [48]. Other amplified regions containing oncogenes, for example AKT3 [22,49] and CCND2 [22,27].…”

Section: Amplificationmentioning

confidence: 99%