TY - JOUR
T1 - Therapeutically promising PNA complementary to a regulatory sequence for c-myc
T2 - Pharmacokinetics in an animal model of human Burkitt's lymphoma
AU - Boffa, Lidia C.
AU - Cutrona, Giovanna
AU - Cilli, Michele
AU - Mariani, Maria Rita
AU - Matis, Serena
AU - Pastorino, Martina
AU - Damonte, Gianluca
AU - Millo, Enrico
AU - Roncella, Silvio
AU - Ferrarini, Manlio
PY - 2005
Y1 - 2005
N2 - 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 14C-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.
AB - 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 14C-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.
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U2 - 10.1089/oli.2005.15.85
DO - 10.1089/oli.2005.15.85
M3 - Article
C2 - 15989423
AN - SCOPUS:22044445097
VL - 15
SP - 85
EP - 93
JO - Oligonucleotides
JF - Oligonucleotides
SN - 1545-4576
IS - 2
ER -