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Regulation of Transgene Expression in Tumor Cells by Exploiting Endogenous Intracellular Signals

Asai, Daisuke and Kang, Jeong-Hun and Toita, Riki and Tsuchiya, Akira and Niidome, Takuro and Nakashima, Hideki and Katayama, Yoshiki (2009) Regulation of Transgene Expression in Tumor Cells by Exploiting Endogenous Intracellular Signals. Nanoscale Research Letters, 4 (3). pp. 229-233.

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Official URL: http://www.springerlink.com/content/k76052060672pl...

Abstract

Recently, we have proposed a novel strategy for a cell-specific gene therapy system based on responses to intracellular signals. In this system, an intracellular signal that is specifically and abnormally activated in the diseased cells is used for the activation of transgene expression. In this study, we used protein kinase C (PKC)α as a trigger to activate transgene expression. We prepared a PKCα-responsive polymer conjugate [PPC(S)] and a negative control conjugate [PPC(A)], in which the phosphorylation site serine (Ser) was replaced with alanine (Ala). The phosphorylation for polymer/DNA complexes was determined with a radiolabel assay using [γ-32P]ATP. PPC(S)/DNA complexes were phosphorylated by the addition of PKCα, but no phosphorylation of the PPC(A)/DNA complex was observed. Moreover, after microinjection of polymer/GFP-encoding DNA complexes into HepG2 cells at cation/anion (C/A) ratios of 0.5 to 2.0, significant expression of GFP was observed in all cases using PPC(S)/DNA complexes, but no GFP expression was observed in the negative control PPC(A)/DNA complex-microinjected cells at C/A ratios of 1.0 and 2.0. On the other hand, GFP expression from PPC(S)/DNA complexes was completely suppressed in cells pretreated with PKCα inhibitor (Ro31-7549). These results suggest that our gene regulation system can be used for tumor cell-specific expression of a transgene in response to PKCα activity.

Item Type:Article
Uncontrolled Keywords:Intracellular signal - Protein kinase C - Gene delivery - Nanoparticle - Tumor
Subjects:Biomedical Science > Nanoscale biological processes
Biomedical Science > Nanotechnology for human health
Biomedical Science > Nanomedicine
ID Code:4182
Deposited By:Lesley Tobin
Deposited On:05 Aug 2009 17:04
Last Modified:05 Aug 2009 17:04

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