Inhibition of rhabdomyosarcoma cell and tumor growth by targeting specificity protein (Sp) transcription factors

Authors

  • Gayathri Chadalapaka,

    1. Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX
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    • G.C. and I.J. contributed equally to this work.

  • Indira Jutooru,

    1. Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX
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    • G.C. and I.J. contributed equally to this work.

  • Sandeep Sreevalsan,

    1. Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX
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  • Satya Pathi,

    1. Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX
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  • Kyounghyun Kim,

    1. Institute for Biosciences and Technology, Texas A&M Health Science Center, Houston, TX
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  • Candy Chen,

    1. Department of Pediatrics, Duke University Medical Center, Durham, NC
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  • Lisa Crose,

    1. Department of Pediatrics, Duke University Medical Center, Durham, NC
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  • Corinne Linardic,

    1. Department of Pediatrics, Duke University Medical Center, Durham, NC
    2. Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC
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  • Stephen Safe

    Corresponding author
    1. Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX
    2. Institute for Biosciences and Technology, Texas A&M Health Science Center, Houston, TX
    • Distinguished Professor of Toxicology, Department of Veterinary Physiology and Pharmacology, Texas A&M University, 4466 TAMU, Vet. Res. Bldg. 410, College Station, Texas 77843-4466
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    • Tel.: 979-845-5988, Fax: 979-862-4929

Errata

This article is corrected by:

  1. Errata: Erratum: Inhibition of rhabdomyosarcoma cell and tumor growth by targeting specificity protein (sp) transcription factors Volume 137, Issue 6, E9, Article first published online: 7 July 2015

  • This work is dedicated to Val and Savannah.

Abstract

Specificity protein (Sp) transcription factors Sp1, Sp3 and Sp4 are highly expressed in rhabdomyosarcoma (RMS) cells. In tissue arrays of RMS tumor cores from 71 patients, 80% of RMS patients expressed high levels of Sp1 protein, whereas low expression of Sp1 was detected in normal muscle tissue. The non-steroidal anti-inflammatory drug (NSAID) tolfenamic acid (TA) inhibited growth and migration of RD and RH30 RMS cell lines and also inhibited tumor growth in vivo using a mouse xenograft (RH30 cells) model. The effects of TA were accompanied by downregulation of Sp1, Sp3, Sp4 and Sp-regulated genes in RMS cells and tumors, and the role of Sp protein downregulation in mediating inhibition of RD and RH30 cell growth and migration was confirmed by individual and combined knockdown of Sp1, Sp3 and Sp4 proteins by RNA interference. TA treatment and Sp knockdown in RD and RH30 cells also showed that four genes that are emerging as individual drug targets for treating RMS, namely c-MET, insulin-like growth factor receptor (IGFR), PDGFRα and CXCR4, are also Sp-regulated genes. These results suggest that NSAIDs such as TA may have potential clinical efficacy in drug combinations for treating RMS patients.

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