Abstract
In Burkitt's lymphoma (BL) cells due to a t(8;14) chromosomal translocation c-myc is often placed in proximity to the Eμ enhancer of the Ig locus and upregulated. We demonstrated that in BL cells a peptide nucleic acid (PNA), complementary to intronic Eμ sequences (PNAEμwt), specifically blocks the expression of the c-myc oncogene under the Eμ enhancer control and inhibits BL cell growth in culture. Here, we investigated whether PNAEμwt 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 PNAEμwt before inoculum and chronic intravenous administration of PNAEμwt to mice already inoculated with BL cells selectively caused increased latency of tumor appearance and decreased final tumor size. Tumors from PNAEμwt-treated animals showed substantial areas of cell necrosis and of c-myc downregulation. Inhibition of tumor growth was specific and was not observed with PNAEμmut carrying sequence mutations and in BL cell lines where the translocated c-myc is not under the control of the Eμ enhancer. These data confirm the potential therapeutic value of PNA targeted to regulatory non-coding regions.
| Original language | English |
|---|---|
| Pages (from-to) | 220-226 |
| Number of pages | 7 |
| Journal | Cancer Gene Therapy |
| Volume | 14 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Feb 2007 |
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Keywords
- Burkitt's lymphoma
- c-myc
- Eμ enhancer
- Gene downregulation
- PNA
ASJC Scopus subject areas
- Cancer Research
- Genetics
Cite this
Inhibition of Burkitt's lymphoma cells growth in SCID mice by a PNA specific for a regulatory sequence of the translocated c-myc. / Boffa, L. C.; Cutrona, G.; Cilli, M.; Matis, S.; Damonte, G.; Mariani, M. R.; Millo, E.; Moroni, M.; Roncella, S.; Fedeli, F.; Ferrarini, M.
In: Cancer Gene Therapy, Vol. 14, No. 2, 02.2007, p. 220-226.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Inhibition of Burkitt's lymphoma cells growth in SCID mice by a PNA specific for a regulatory sequence of the translocated c-myc
AU - Boffa, L. C.
AU - Cutrona, G.
AU - Cilli, M.
AU - Matis, S.
AU - Damonte, G.
AU - Mariani, M. R.
AU - Millo, E.
AU - Moroni, M.
AU - Roncella, S.
AU - Fedeli, F.
AU - Ferrarini, M.
PY - 2007/2
Y1 - 2007/2
N2 - In Burkitt's lymphoma (BL) cells due to a t(8;14) chromosomal translocation c-myc is often placed in proximity to the Eμ enhancer of the Ig locus and upregulated. We demonstrated that in BL cells a peptide nucleic acid (PNA), complementary to intronic Eμ sequences (PNAEμwt), specifically blocks the expression of the c-myc oncogene under the Eμ enhancer control and inhibits BL cell growth in culture. Here, we investigated whether PNAEμwt 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 PNAEμwt before inoculum and chronic intravenous administration of PNAEμwt to mice already inoculated with BL cells selectively caused increased latency of tumor appearance and decreased final tumor size. Tumors from PNAEμwt-treated animals showed substantial areas of cell necrosis and of c-myc downregulation. Inhibition of tumor growth was specific and was not observed with PNAEμmut carrying sequence mutations and in BL cell lines where the translocated c-myc is not under the control of the Eμ enhancer. These data confirm the potential therapeutic value of PNA targeted to regulatory non-coding regions.
AB - In Burkitt's lymphoma (BL) cells due to a t(8;14) chromosomal translocation c-myc is often placed in proximity to the Eμ enhancer of the Ig locus and upregulated. We demonstrated that in BL cells a peptide nucleic acid (PNA), complementary to intronic Eμ sequences (PNAEμwt), specifically blocks the expression of the c-myc oncogene under the Eμ enhancer control and inhibits BL cell growth in culture. Here, we investigated whether PNAEμwt 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 PNAEμwt before inoculum and chronic intravenous administration of PNAEμwt to mice already inoculated with BL cells selectively caused increased latency of tumor appearance and decreased final tumor size. Tumors from PNAEμwt-treated animals showed substantial areas of cell necrosis and of c-myc downregulation. Inhibition of tumor growth was specific and was not observed with PNAEμmut carrying sequence mutations and in BL cell lines where the translocated c-myc is not under the control of the Eμ enhancer. These data confirm the potential therapeutic value of PNA targeted to regulatory non-coding regions.
KW - Burkitt's lymphoma
KW - c-myc
KW - Eμ enhancer
KW - Gene downregulation
KW - PNA
UR - http://www.scopus.com/inward/record.url?scp=33846248757&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33846248757&partnerID=8YFLogxK
U2 - 10.1038/sj.cgt.7701002
DO - 10.1038/sj.cgt.7701002
M3 - Article
C2 - 17053816
AN - SCOPUS:33846248757
VL - 14
SP - 220
EP - 226
JO - Cancer Gene Therapy
JF - Cancer Gene Therapy
SN - 0929-1903
IS - 2
ER -