Details

Autor(en) / Beteiligte

• Boffa, Lidia C.
• Cutrona, Giovanna
• Cilli, Michele
• Mariani, Maria Rita
• Matis, Serena
• Pastorino, Martina
• Damonte, Gianluca
• Millo, Enrico
• Roncella, Silvio
• Ferrarini, Manlio

Titel

Therapeutically Promising PNA Complementary to a Regulatory Sequence for c-myc: Pharmacokinetics in an Animal Model of Human Burkitt's Lymphoma

Ist Teil von

• Oligonucleotides, 2005-01, Vol.15 (2), p.85-93

Ort / Verlag

United States: Mary Ann Liebert, Inc

Erscheinungsjahr

2005

Quelle

MEDLINE

Beschreibungen/Notizen

• In Burkitt's lymphoma (BL) cells c- myc is often translocated in proximity to the Eµ enhancer of the Ig gene locus. This translocation causes c- myc hyperexpression and an increase in the cells' proliferative capacity. A peptide nucleic acid (PNA) complementary to enhancer Eµ intronic sequence (PNAEµ), linked to a nuclear localization signal (NLS), selectively and specifically blocks the expression of the c- myc oncogene under Eµ control in vitro , suggesting potential therapeutic use. To explore this issue further, we have determined the pharmacokinetics of 14 C-labeled PNAEµ in SCID mice where a human tumor is established by inoculation of cells from a BL cell line. The data demonstrate that the compound has a relatively long life in vivo in tissues and, in particular, in BL tumor mass. Furthermore, in this animal model, PNAEµ shows low or no toxicity. All these results are in favor of a successful preclinical application in a BL human tumor animal model of a PNA targeting a regulatory, nontranscribed DNA sequence that can selectively inhibit the hyperexpression of a translocated gene linked to neoplastic cell expansion.