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Inhibition of Burkitt's lymphoma cells growth in SCID mice by a PNA specific for a regulatory sequence of the translocated c-myc

Cancer Gene Therapy volume 14, pages 220–226 (2007)Cite this article

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.

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Acknowledgements

This work was supported by grants by Associazione Italiana per la Ricerca sul Cancro (MF), Project AIDS Grant 30D-30 (MF), Fondo Investimenti Ricerca di Base (FIRB) RBAU01R5SE (MF, LCB); CIPE, 2004:CBA Project (GC, LCB); National Research Program ‘Technologies in Oncology’ Theme12 (MF, LCB), Salute 2005 (LCB, GC); (AIL): Associazione Italiana Leucemie, Sez. Francesca Lanzone, SP (SR); RBNE01TBTR-003 (U Benatti); Istituto Superiore di Sanità. We thank Dr EM Carpaneto for reviewing the manuscript. We also acknowledge the excellent technical support of Ms Lorella Pecunia in histological preparations and of the PDTC, The Rockefeller University, New York, NY in PNA characterization and purification.

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Authors and Affiliations

  1. SC. Oncologia Medica C, Istituto Nazionale per la Ricerca sul Cancro, IST, Genova, Italy

    L C Boffa, G Cutrona, S Matis, M R Mariani & M Ferrarini

  2. SS. Sperimentazione su Modelli Animali, Istituto Nazionale per la Ricerca sul Cancro, IST, Genova, Italy

    M Cilli

  3. DOBIG, Biochemistry Section, and Center of Excellence for Biomedical Research, Università degli Studi di Genova, Genova, Italy

    S Matis & M Ferrarini

  4. DIMES, Biochemistry Section, and Center of Excellence for Biomedical Research, Università degli Studi di Genova, Genova, Italy

    G Damonte & E Millo

  5. UO Anatomia ed Istologia Patologica, ASL5, La Spezia, Italy

    M Moroni, S Roncella & F Fedeli

Authors
  1. L C Boffa
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  2. G Cutrona
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  3. M Cilli
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  4. S Matis
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  5. G Damonte
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  6. M R Mariani
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  7. E Millo
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  8. M Moroni
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  9. S Roncella
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  10. F Fedeli
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  11. M Ferrarini
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Correspondence to L C Boffa.

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Boffa, L., Cutrona, G., Cilli, M. et al. Inhibition of Burkitt's lymphoma cells growth in SCID mice by a PNA specific for a regulatory sequence of the translocated c-myc. Cancer Gene Ther 14, 220–226 (2007). https://doi.org/10.1038/sj.cgt.7701002

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