Gene regulation by decoy approach (II): Development of photo-cross-linked oligonucleotides duplex as a decoy DNA for estrogen receptor.
We have developed a photo-cross-linked oligonucleotide (clip-ODN) for a novel type of gene regulator molecule. Here, we examined the ability of the clip-ODN as a decoy DNA on regulation of the transcriptional activity of estrogen receptor (ER). A photo-cross-linking reagent, 4,5',8-[4'-(aminoethyl-amino) methyl]-trimethylpsoralen (aeAMT) was conjugated with an ODN at the 5'-end, and the aeAMT was cross-linked with the thymine residue of the complementary oligonucleotide upon UVA irradiation (365nm). The clip-ODN drastically inhibited the proliferation of breast cancer cell line (MCF-7) than non-cliped one in a sequence specific manner. This finding revealed that photo-cross-linking of double stranded ODN improve the regulatory ability as a decoy DNA, and clip-ODN may be a valuable tool in gene therapy protocols for inhibiting breast cancer cells' proliferation.
Yamayoshi
Asako
A
Department of Biomolecular Engineering, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto, 606-8585, Japan.
Shimazu
Noriko
N
Higuchi
Maiko
M
Kobori
Akio
A
Murakami
Akira
A
D001943:Breast Neoplasms / Q000628:therapy*; D045744:Cell Line, Tumor; D003432:Cross-Linking Reagents / Q000737:chemistry; D005260:Female; D005786:Gene Expression Regulation; D015316:Genetic Therapy; D006576:Heterocyclic Compounds, 4 or More Rings / Q000737:chemistry; D006801:Humans; D009838:Oligodeoxyribonucleotides / Q000737:chemistry*; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors*; D014158:Transcription, Genetic; D014466:Ultraviolet Rays
C506010:4,5',8-(4-Aminoethylaminomethyl)-trioxalen; D003432:Cross-Linking Reagents; D006576:Heterocyclic Compounds, 4 or More Rings; D009838:Oligodeoxyribonucleotides; D011960:Receptors, Estrogen