IGF-1 receptor inhibition by picropodophyllin in medulloblastoma

Sachiko Ohshima-Hosoyama, Tohru Hosoyama, Laura D. Nelon, Charles Keller

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

The insulin-like growth factor-1 receptor (Igf1r) is a multifunctional membrane-associated tyrosine kinase associated with regulation of transformation, proliferation, differentiation and apoptosis. Increased IGF pathway activity has been reported in human and murine medulloblastoma. Tumors from our genetically-engineered medulloblastoma mouse model over-express Igf1r, and thus this mouse model is a good platform with which to study the role of Igf1r in tumor progression. We hypothesize that inhibition of IGF pathway in medulloblastoma can slow or inhibit tumor growth and metastasis. To test our hypothesis, we tested the role of IGF in tumor growth in vitro by treatment with the tyrosine kinase small molecule inhibitor, picropodophyllin (PPP), which strongly inhibits the IGF pathway. Our results demonstrate that PPP-mediated downregulation of the IGF pathway inhibits mouse tumor cell growth and induces apoptotic cell death in vitro in primary medulloblastoma cultures that are most reflective of tumor cell behavior in vivo.

Original languageEnglish (US)
Pages (from-to)727-732
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume399
Issue number4
DOIs
StatePublished - Sep 1 2010

Keywords

  • Apoptosis
  • Insulin-like growth factor-1 receptor
  • Medulloblastoma
  • Picropodophyllin
  • Tumor growth

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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