A chimeric fusion of the hASH1 and EZH2 promoters mediates high and specific reporter and suicide gene expression and cytotoxicity in small cell lung cancer cells

Cancer Gene Therapy
T T PoulsenH S Poulsen

Abstract

Transcriptionally targeted gene therapy is a promising experimental modality for treatment of systemic malignancies such as small cell lung cancer (SCLC). We have identified the human achaete-scute homolog 1 (hASH1) and enhancer of zeste homolog 2 (EZH2) genes as highly upregulated in SCLC compared to a panel of representative normal tissues. Here, we evaluate the use of regulatory regions from the hASH1- and EZH2-promoter regions alone and in combination for suicide gene therapy of SCLC. Two hASH1-promoter regions comprising 0.3 and 0.7 kb immediately upstream of (and including) the transcription start site were tested. Both constructs induced reporter gene activity (up to sevenfold SV40-promoter activity) in all tested classic (hASH1 positive) SCLC and in two hASH1-negative SCLC cell lines, whereas gene activity was low or absent (<4% of SV40 activity) in one hASH1-negative SCLC and in all control cell lines tested. To evaluate its therapeutic potential, the 0.7 kb hASH1 proximal-promoter region was evaluated for cytotoxicity in a suicide gene assay. The construct induced SCLC cytotoxicity at levels equivalent to those observed with the SV40 promoter, while control cells remained unaffected by the treatment. Analogously, a 1....Continue Reading

References

Jan 1, 1987·Journal of Cancer Research and Clinical Oncology·G BeplerK Havemann
Apr 22, 1993·International Journal of Cancer. Journal International Du Cancer·K RygaardM Spang-Thomsen
Jan 23, 1993·Biochimica Et Biophysica Acta·F Franco del AmoT Gridley
Dec 15, 1996·Developmental Biology·S Verma-KurvariJ E Johnson
Nov 5, 1999·The Journal of Pathology·J YuanK Strebhardt
Mar 4, 2000·International Journal of Cancer. Journal International Du Cancer·N InaseY Yoshizawa
Nov 15, 2001·Proceedings of the National Academy of Sciences of the United States of America·A BhattacharjeeM Meyerson
Feb 7, 2002·The European Respiratory Journal·E BrambillaY Shimosato
Apr 10, 2002·Molecular and Cellular Biology·Virote SriuranpongDouglas W Ball
Oct 11, 2002·Nature·Sooryanarayana VaramballyArul M Chinnaiyan
Apr 25, 2003·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Lasse Tengbjerg HansenMogens Spang-Thomsen
Sep 23, 2003·Proceedings of the National Academy of Sciences of the United States of America·Celina G KleerArul M Chinnaiyan
Dec 6, 2003·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Shi-Xu JiangIsao Okayasu
Oct 22, 2004·The EMBO Journal·Carlos M ParrasFrançois Guillemot
Feb 8, 2005·Clinical Lung Cancer·Thomas T PoulsenHans S Poulsen
Dec 7, 2005·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Ingeborg M BachmannLars A Akslen
Dec 14, 2005·Current Treatment Options in Oncology·Kristen Keon Ciombor, Caio Max S Rocha Lima
Aug 30, 2006·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Colin S CooperShu-Jun Cheng

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Citations

Apr 8, 2010·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Camilla L ChristensenHans S Poulsen
Oct 20, 2010·International Journal of Nanomedicine·Torben GjettingHans Skovgaard Poulsen
Apr 21, 2009·Expert Review of Anticancer Therapy·Camilla L ChristensenHans S Poulsen
Apr 23, 2013·The Journal of Investigative Dermatology·Diego L VialeM Veronica Lopez
Mar 1, 2018·Applied Immunohistochemistry & Molecular Morphology : AIMM·Pinuccia FavianaLaura Boldrini
Jul 17, 2018·Doklady. Biochemistry and Biophysics·I V AlekseenkoE D Sverdlov
Mar 19, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Roza ZandiHans Skovgaard Poulsen

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