Open AccessProtein kinase Cα‐responsive polymeric carrier: its application for gene delivery into human cancers
Author(s) -
Tomiyama Tetsuro,
Kang JeongHun,
Toita Riki,
Niidome Takuro,
Katayama Yoshiki
Publication year - 2009
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2009.01198.x
Subject(s) - transfection , protein kinase c , gene delivery , cancer cell , serine , cancer research , phosphorylation , cell culture , kinase , microbiology and biotechnology , chemistry , a549 cell , protein kinase a , luciferase , biology , cancer , cell , gene , biochemistry , genetics
For cancer‐targeting gene delivery, we applied a protein kinase C (PKC)α‐responsive polymeric carrier to human cancers (U‐87 MG [human glioblastoma‐astrocytoma, epithelial‐like cell line] and A549 [human lung adenocarcinoma epithelial cell line]). Two polymers, one a PKCα‐responsive polymer (PPC[S]) containing the phosphorylation site serine, and the other a negative control polymer (PPC[A]), in which the serine was substituted with alanine, were synthesized. No cytotoxicity of the polymer was identified. When the complexes were transfected into cancer cells or tissues in which PKCα was hyper‐activated, the luciferase expression from the PPC(S)/plasmid (pDNA) complex was higher than that from the PPC(A)/pDNA complex. These results show that the phosphorylation of complex by PKCα in cancer cells leads to high gene expression and that our system can be used as a human cancer cell–targeting gene delivery system. ( Cancer Sci 2009)