Inhibition of Burkitt's lymphoma cells growth in SCID mice by a PNA specific for a regulatory sequence of the translocated c-myc.
In Burkitt's lymphoma (BL) cells due to a t(8;14) chromosomal translocation c-myc is often placed in proximity to the Emu enhancer of the Ig locus and upregulated. We demonstrated that in BL cells a peptide nucleic acid (PNA), complementary to intronic Emu sequences (PNAEmuwt), specifically blocks the expression of the c-myc oncogene under the Emu enhancer control and inhibits BL cell growth in culture. Here, we investigated whether PNAEmuwt was also able to block tumor growth in SCID mice inoculated with human BL cell lines. After subcutaneous inoculum in mice BL cells reproducibly form tumors. Both pre-treatment of BL cells with PNAEmuwt before inoculum and chronic intravenous administration of PNAEmuwt to mice already inoculated with BL cells selectively caused increased latency of tumor appearance and decreased final tumor size. Tumors from PNAEmuwt-treated animals showed substantial areas of cell necrosis and of c-myc downregulation. Inhibition of tumor growth was specific and was not observed with PNAEmumut carrying sequence mutations and in BL cell lines where the translocated c-myc is not under the control of the Emu enhancer. These data confirm the potential therapeutic value of PNA targeted to regulatory non-coding regions.
Boffa
L C
LC
SC. Oncologia Medica C, Istituto Nazionale per la Ricerca sul Cancro, IST, Largo R. Benzi, GE 10 Genoa 16132, Italy. lidia.boffa@istge.it
Cutrona
G
G
Cilli
M
M
Matis
S
S
Damonte
G
G
Mariani
M R
MR
Millo
E
E
Moroni
M
M
Roncella
S
S
Fedeli
F
F
Ferrarini
M
M
D000818:Animals; D001483:Base Sequence; D002051:Burkitt Lymphoma / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects*; D016259:Genes, myc; D007150:Immunohistochemistry; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D020135:Peptide Nucleic Acids / Q000737:chemistry / Q000494:pharmacology*; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic
D020135:Peptide Nucleic Acids; D012333:RNA, Messenger