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

Publication ,  Journal Article
Chadalapaka, G; Jutooru, I; Sreevalsan, S; Pathi, S; Kim, K; Chen, C; Crose, L; Linardic, C; Safe, S
Published in: Int J Cancer
February 15, 2013

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.

Duke Scholars

Published In

Int J Cancer

DOI

EISSN

1097-0215

Publication Date

February 15, 2013

Volume

132

Issue

4

Start / End Page

795 / 806

Location

United States

Related Subject Headings

  • ortho-Aminobenzoates
  • Xenograft Model Antitumor Assays
  • Sp Transcription Factors
  • Rhabdomyosarcoma
  • Receptors, Somatomedin
  • Receptors, CXCR4
  • Receptor, Platelet-Derived Growth Factor alpha
  • RNA, Small Interfering
  • RNA Interference
  • Proto-Oncogene Proteins c-met
 

Citation

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Chicago
ICMJE
MLA
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Chadalapaka, G., Jutooru, I., Sreevalsan, S., Pathi, S., Kim, K., Chen, C., … Safe, S. (2013). Inhibition of rhabdomyosarcoma cell and tumor growth by targeting specificity protein (Sp) transcription factors. Int J Cancer, 132(4), 795–806. https://doi.org/10.1002/ijc.27730
Chadalapaka, Gayathri, Indira Jutooru, Sandeep Sreevalsan, Satya Pathi, Kyounghyun Kim, Candy Chen, Lisa Crose, Corinne Linardic, and Stephen Safe. “Inhibition of rhabdomyosarcoma cell and tumor growth by targeting specificity protein (Sp) transcription factors.Int J Cancer 132, no. 4 (February 15, 2013): 795–806. https://doi.org/10.1002/ijc.27730.
Chadalapaka G, Jutooru I, Sreevalsan S, Pathi S, Kim K, Chen C, et al. Inhibition of rhabdomyosarcoma cell and tumor growth by targeting specificity protein (Sp) transcription factors. Int J Cancer. 2013 Feb 15;132(4):795–806.
Chadalapaka, Gayathri, et al. “Inhibition of rhabdomyosarcoma cell and tumor growth by targeting specificity protein (Sp) transcription factors.Int J Cancer, vol. 132, no. 4, Feb. 2013, pp. 795–806. Pubmed, doi:10.1002/ijc.27730.
Chadalapaka G, Jutooru I, Sreevalsan S, Pathi S, Kim K, Chen C, Crose L, Linardic C, Safe S. Inhibition of rhabdomyosarcoma cell and tumor growth by targeting specificity protein (Sp) transcription factors. Int J Cancer. 2013 Feb 15;132(4):795–806.
Journal cover image

Published In

Int J Cancer

DOI

EISSN

1097-0215

Publication Date

February 15, 2013

Volume

132

Issue

4

Start / End Page

795 / 806

Location

United States

Related Subject Headings

  • ortho-Aminobenzoates
  • Xenograft Model Antitumor Assays
  • Sp Transcription Factors
  • Rhabdomyosarcoma
  • Receptors, Somatomedin
  • Receptors, CXCR4
  • Receptor, Platelet-Derived Growth Factor alpha
  • RNA, Small Interfering
  • RNA Interference
  • Proto-Oncogene Proteins c-met