Effects in live cells of a c-myc anti-gene PNA linked to a nuclear localization signal.
Peptide nucleic acids (PNA) are synthetic homologs of nucleic acids in which the phosphate-sugar polynucleotide backbone is replaced by a flexible polyamide. In this study, a PNA construct was employed as an anti-gene agent in intact cells in culture. The cell lines studied were derived from Burkitt's lymphomas (BL) that presented a translocated and hyperexpressed c-myc oncogene. A 17-mer anti-myc PNA, complementary to a unique sequence located at the beginning of the second exon of the oncogene, and was covalently linked at its N terminus to a nuclear localization signal (NLS) (PNA-myc(wt)-NLS). When BL cells were exposed to PNA-myc(wt)-NLS, the anti-gene construct was localized predominantly in the cell nuclei and a rapid consequent downregulation of c-myc expression occurred. Under these conditions, both completion of a productive cell cycle and apoptosis were inhibited.
Cutrona
G
G
Servizi di Immunologia Clinica, National Cancer Institute, Genoa, Italy.
Carpaneto
E M
EM
Ulivi
M
M
Roncella
S
S
Landt
O
O
Ferrarini
M
M
Boffa
L C
LC
D000952:Antigens, Polyomavirus Transforming / Q000378:metabolism; D017209:Apoptosis; D016923:Cell Death; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D016259:Genes, myc / Q000235:genetics*; D006801:Humans; D018613:Microscopy, Confocal; D009685:Nuclear Envelope / Q000187:drug effects / Q000378:metabolism; D019913:Nuclear Localization Signals / Q000235:genetics*; D020135:Peptide Nucleic Acids / Q000494:pharmacology*; D010957:Plasmids; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D014407:Tumor Cells, Cultured
D000952:Antigens, Polyomavirus Transforming; D019913:Nuclear Localization Signals; D020135:Peptide Nucleic Acids; D016271:Proto-Oncogene Proteins c-myc