Radiosensitization of malignant glioma cells through overexpression of dominant-negative EGFR-CD533

Lammering, Guido; Valerie, Kristoffer; Lin, Peck Sun; Mikkelsen, Ross B.; Hewit, Theodore H.; Schmidt‐Ullrich, Rupert

doi:10.1016/s0360-3016(00)80289-8

Cited by 31 publications

(44 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Gene therapy targeting TK domain in glioma therapy EGFR gene consists of 28 exons and encodes a 170 kDa of glycoprotein, comprising an extracellular region (encoded by exons 1-16), a membrane spanning region (encoded by exon 17) and an intracellular region (encoded by exons [18][19][20][21][22][23][24][25][26][27][28]. 19 The extracellular portion of EGFR is Figure 5 Compare to the group of PBS and psiRNA-scr, tumor growth in nude mice in the group of psiRNA-EGFR and panti-EGFR were inhibited (Po0.001) (a), EGFR expression of tumors was downregulated (b), GFAP expression was upregulated (c), apoptosis cells become obvious by TUNEL staining (d), and PCNA expression was downregulated (Po0.001) (e).…”

Section: Discussionmentioning

confidence: 99%

“…The antisense, dominant-negative or EGFR TK inhibitor could effectively inhibit tumor growth, induce apoptosis and cell cycle arrest, and enhance the radiosensitization of gliomas. [25][26][27][28] Using an antisense construct complementary to the 3 0 -coding region of EGFR mRNA (AS-3 0 ,552 bp), Pu et al 25 have demonstrated that exogenous antisense EGFR cDNA can successfully inhibit proliferation and induce apoptosis in C6 glioma cells in vitro, and stereotactically delivery of lipofectin-mediated antisense construct can prolong survival time of tumor-bearing rats. In addition, studies by Ng have demonstrated that antisense EGFR construct transfected into U87 glioma cell can impair the proliferation, reduce the soft agarose growth activities, induce G0/G1 arrest, and upregulate the expression of GFAP.…”

Section: Biological Changes By Silenced Egfr Expressionmentioning

confidence: 99%

See 1 more Smart Citation

Suppression of EGFR expression by antisense or small interference RNA inhibits U251 glioma cell growth in vitro and in vivo

et al. 2006

Cancer Gene Ther

View full text Add to dashboard Cite

Epidermal growth factor receptor (EGFR) had been reported as one of the major responsible genes for malignant progression and phenotype reversion of gliomas, and has been used as one of the most important therapeutic targets. In the present study, small interference RNA (siRNA) and antisense EGFR expression constructs, which target sequences of human EGFR catalytic domain (2400-2420) and the 3 0 -coding region, respectively, were used to examine the growth inhibition effects on U251 glioma cells. Cell growth was significantly inhibited and G2/M arrest was observed in antisense-and siRNA-treated groups. Matrigel matrix demonstrated spotted cell clustering pattern in antisense-and siRNA-transfected U251 cells, indicating poor cell growth activities. In addition, the tumor volumes in U251 subcutaneous mice model treated with antisense and siRNA were significantly smaller than those treated with control siRNA and phosphate-buffered saline. Also, glial fibrillary acidic protein expression was upregulated in antisense-and siRNA-treated groups than the control groups. Our results demonstrated that antisense-or siRNA-targeting intracellular region of EGFR can inhibit EGFR expression, exerted growth inhibition effect on U251 glioma cells in vitro and in vivo. Consequently, siRNA expression plasmid-mediated gene therapy would be a new strategy in treatment of gliomas.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Biological Changes By Silenced Egfr Expressionmentioning

confidence: 99%

Suppression of EGFR expression by antisense or small interference RNA inhibits U251 glioma cell growth in vitro and in vivo

et al. 2006

Cancer Gene Ther

View full text Add to dashboard Cite

show abstract

“…A multiplicity of infection (MOI) of 3 was found to be optimal, as described previously (24). Mock transductions were carried out under conditions identical to those used for the Ad transduction, except for the addition of Ad preparations.…”

Section: Methodsmentioning

confidence: 99%

“…Forty-eight hours after transduction with 3 MOI of Ad-LacZ or Ad-EGFRvIII or the combination of Ad-LacZ ϩ Ad-EGFR-CD533 or Ad-EGFRvIII ϩ Ad-EGFR-CD533 at 3 MOI for each Ad vector, cells were harvested, and 500 cells were plated for each group into 4-well 60-mm dishes for clonogenic survival. Cells were incubated under standard culture conditions for 14 days and stained with crystal violet, and colonies containing Ն50 cells were counted to determine the plating efficiency (24,27).…”

Section: Methodsmentioning

confidence: 99%

Inhibition of the Type III Epidermal Growth Factor Receptor Variant Mutant Receptor by Dominant-Negative EGFR-CD533 Enhances Malignant Glioma Cell Radiosensitivity

Lammering

Hewit

Holmes

et al. 2004

Clinical Cancer Research

View full text Add to dashboard Cite

show abstract

“…(1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14) ErbB-2, a member of the EGFR family, is also overexpressed in 30% of breast tumors as well as in a significant number of other cancers. (15,16) Blockade of the EGFRmediated signaling pathway enhances the sensitivity of tumor cells to radiation and several chemotherapeutic agents.…”

mentioning

confidence: 99%

Heat shock protein 90 inhibitor 17‐allylamino‐17‐demethoxygeldanamycin potentiates the radiation response of tumor cells grown as monolayer cultures and spheroids by inducing apoptosis

et al. 2005

View full text Add to dashboard Cite

Activation of the PI3K-Akt pathway is known to induce tumor radioresistance. In the current study, we examined the ability of 17AAG, which decreases the levels of Hsp90 client proteins including components of the PI3K-Akt pathway, to sensitize radioresistant human squamous cell carcinoma cells to Xirradiation. Human squamous cell carcinoma cell lines (SQ20B, SCC61 and SCC13) were incubated for 16 h at 37°°°°C in medium containing 17AAG. Radiation sensitivity was determined by clonogenic assays, and protein levels were examined by western blotting. Apoptosis was determined in monolayer cells by AO/EB double staining and in spheroids using the TdT-mediated dUTP nick end labeling assay. 17AAG (0.2 µ µ µ µM) enhanced the radiosensitivity more effectively in radioresistant SQ20B and SCC13 cells than in radiosensitive SCC61 cells. However, in all three cell lines, 17AAG increased radiation-induced apoptosis by reducing the expression of EGFR and ErbB-2 and inhibiting the phosphorylation of Akt. Furthermore, 17AAG (1 µ µ µ µM) sensitized SQ20B spheroids to radiation, and inhibition of Akt activation by 17AAG increased radiation-induced apoptosis in spheroids. The findings suggest that 17AAG effectively sensitizes radioresistant cells to radiation by inhibiting the PI3K-Akt pathway. Targeting the PI3K-Akt pathway with 17AAG could be a useful strategy for radiosensitization of carcinomas. (Cancer Sci 2005; 96: 911-917) R adiation therapy is commonly used for squamous cell carcinoma of the head and neck because of its minimal cosmetic effects and its ability to preserve voice in laryngeal cancer. However, treatment failure correlates with a poorer prognosis and decreased patient survival.The EGFR family contributes to resistance to radiation and chemotherapy in many human tumors, including head and neck cancer.(1-14) ErbB-2, a member of the EGFR family, is also overexpressed in 30% of breast tumors as well as in a significant number of other cancers. (15,16) Blockade of the EGFRmediated signaling pathway enhances the sensitivity of tumor cells to radiation and several chemotherapeutic agents.The PI3K-Akt pathway is a major downstream pathway initiated by activation of the EGFR family members. (17)(18)(19)(20)(21) This pathway plays an important role in cell growth and survival. (22,23) The serine/threonine kinase Akt (also known as protein kinase B) is thought to be a downstream target of PI3K. Akt activation is responsible for desensitizing cells to apoptotic stimuli. This occurs by regulation of the transcriptional activity of both Forkhead family members (24,25) and NF-κB, (26,27) and through phosphorylation and inactivation of the apoptotic machinery including Bcl-2 homolog, Bad (28,29) and caspase-9.(30) Furthermore, Akt is amplified or overexpressed in a wide variety of human tumors.(31-33) PTEN, a tumor suppressor gene, is thought to negatively regulate the PI3K-Akt pathway.(34-36) Mutations causing PTEN to be functionally inactive are frequently detected in many human cancers and enhance Akt activity.(37) Akt acti...

show abstract

Radiosensitization of malignant glioma cells through overexpression of dominant-negative EGFR-CD533

Cited by 31 publications

References 0 publications

Suppression of EGFR expression by antisense or small interference RNA inhibits U251 glioma cell growth in vitro and in vivo

Suppression of EGFR expression by antisense or small interference RNA inhibits U251 glioma cell growth in vitro and in vivo

Inhibition of the Type III Epidermal Growth Factor Receptor Variant Mutant Receptor by Dominant-Negative EGFR-CD533 Enhances Malignant Glioma Cell Radiosensitivity

Heat shock protein 90 inhibitor 17‐allylamino‐17‐demethoxygeldanamycin potentiates the radiation response of tumor cells grown as monolayer cultures and spheroids by inducing apoptosis

Contact Info

Product

Resources

About