Sustained gene transfer and enhanced cell death following glucosylated-PEI-mediated p53 gene transfer with photochemical internalisation in p53-mutated head and neck carcinoma cells

Ndoye, Alioune; Bouali, Sanae; Dolivet, Gilles; Leroux, Agnès; Erbacher, Patrick; Behr, Jean Paul; Berg, Kristian; Guillemin, François; Merlin, Jean Louis

doi:10.3892/ijo.25.6.1575

Cited by 10 publications

(10 citation statements)

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“…51 The direct delivery approach in the context of either viral or non-viral vectors is in general applicable to accessible solid tumors, thus limiting the field of action to a few malignancies, for example, melanoma, head and neck tumors, mesothelioma and so on. However, some of these malignancies are resistant to conventional therapies, and gene therapy trials are warranted, to delineate new potential treatments.…”

Section: Discussionmentioning

confidence: 99%

Saporin as a novel suicide gene in anticancer gene therapy

et al. 2006

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We used a non-viral gene delivery approach to explore the potential of the plant saporin (SAP) gene as an alternative to the currently employed suicide genes in cancer therapy. Plasmids expressing cytosolic SAP were generated by placing the region encoding the mature plant ribosome-inactivating protein under the control of cytomegalovirus (CMV) or simian virus 40 (SV40) promoters. Their ability to inhibit protein synthesis was first tested in cultured tumor cells co-transfected with a luciferase reporter gene. In particular, SAP expression driven by CMV promoter (pCI-SAP) demonstrated that only 10 ng of plasmid per 1.6 Â 10 4 B16 cells drastically reduced luciferase activity to 18% of that in control cells. Direct intratumoral injection of pCI-SAP complexed with either lipofectamine or N-(2,3-dioleoyloxy-1-propyl) trimethylammonium methyl sulfate (DOTAP) in B16 melanoma-bearing mice resulted in a noteworthy attenuation of tumor growth. This antitumor effect was increased in mice that received repeated intratumoral injections. A SAP catalytic inactive mutant (SAP-KQ) failed to exert any antitumor effect demonstrating that this was specifically owing to the SAP N-glycosidase activity. Our overall data strongly suggest that the gene encoding SAP, owing to its rapid and effective action and its independence from the proliferative state of target cells might become a suitable candidate suicide gene for oncologic applications.

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Section: Discussionmentioning

confidence: 99%

Saporin as a novel suicide gene in anticancer gene therapy

et al. 2006

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“…Reduction of cell proliferation was achieved by the induction of a G1 arrest of the cell cycle which led to a decrease of S phase cells. Remarkably, this G1 arrest has to be mediated through mechanisms independent of TP53 and could accordingly not be detected after irradiation of FaDu cells, as TP53 is mutated in FaDu cells [21,28,30]. Recently, a role for p27 and p21 as well as cyclin dependent kinase 2 (CDK2), CDK4, CDK6, cyclin D1, cyclin D3, and Rb2/p130 in the ZD1839-induced G1 arrest has been suggested [9,13,25].…”

Section: Discussionmentioning

confidence: 99%

Radiosensitivity of Tumor Cell Lines after Pretreatment with the EGFR Tyrosine Kinase Inhibitor ZD1839 (Iressa®)

et al. 2005

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“…20,21 Western blot Cells were exposed to epidermal growth factor (EGF, 100 ng ml À1 ) for 5 min (Roche Diagnostics, Penzberg, Germany). Western blots were carried out with total protein extracted from cells as already described using monoclonal antibody directed against PTEN, pPTEN, P53, AKT, phosphorylated-AKT (pAKT), GSK3b, pGSK3b, P70S6K, pP70S6K, ERK1/2, pERK1/2, BAX and tubulin 22 (Table 1).…”

Section: Mrna Expression Analysismentioning

confidence: 99%

P53 and PTEN expression contribute to the inhibition of EGFR downstream signaling pathway by cetuximab

Bouali

Ramacci

et al. 2009

Cancer Gene Ther

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Cetuximab (Erbitux) is an anti-epidermal growth factor receptor (EGFR) monoclonal antibody whose activity is related to the inhibition of EGFR downstream signaling pathways. P53 and phosphatase and tensin homologue deleted on chromosome 10 (PTEN) have been reported to control the functionality of PI3K/AKT signaling. In this study we evaluated whether reintroducing P53 using non-viral gene transfer enhances PTEN-mediated inhibition of PI3K/AKT signaling by cetuximab in PC3 prostate adenocarcinoma cell line bearing p53 and pten mutations. Signaling phosphoproteins expression was analyzed using Bio-Plex phosphoprotein array and western blot. Apoptosis induction was evaluated from BAX expression, caspase-3 activation and DNA fragmentation analyses. The results presented show that p53 and pten gene transfer additionally mediated cell growth inhibition and apoptosis induction by restoral of signaling functionality, which enabled the control of PI3K/AKT and MAPKinase signaling pathways by cetuximab in PC3 cells. These results highlight the interest of the analysis of signaling phosphoproteins expression as molecular predictive markers for response to cetuximab and show that p53 and pten mutations could be key determinants of cell response to cetuximab through the functional impact of these mutations on cell signaling.

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Sustained gene transfer and enhanced cell death following glucosylated-PEI-mediated p53 gene transfer with photochemical internalisation in p53-mutated head and neck carcinoma cells

Cited by 10 publications

References 0 publications

Saporin as a novel suicide gene in anticancer gene therapy

Saporin as a novel suicide gene in anticancer gene therapy

Radiosensitivity of Tumor Cell Lines after Pretreatment with the EGFR Tyrosine Kinase Inhibitor ZD1839 (Iressa®)

P53 and PTEN expression contribute to the inhibition of EGFR downstream signaling pathway by cetuximab

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