Herstatin, an autoinhibitor of the epidermal growth factor receptor family, blocks the intracranial growth of glioblastoma

Julia Staverosky, Leslie Muldoon, Shuhua Guo, Adam J. Evans, Edward Neuwelt, Gail M. Clinton

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Purpose: Herstatin, an autoinhibitor of the epidermal growth factor (EGF) receptor family, was evaluated for efficacy against human glioblastoma in vitro and in vivo in a rat intracranial model. Experimental Design: Glioblastoma controlled by EGF receptor (EGFR; U87MG) or by the truncated mutant, ΔEGFR (U87MG/Δ), were transfected with Herstatin and evaluated for in vitro and in vivo growth in nude rat brain. Cells treated with purified Herstatin in vitro were evaluated for growth and signal transduction. Results: Herstatin expression prevented tumor formation by U87MG and purified Herstatin inhibited their growth in vitro in a dose-responsive fashion, whereas in vivo and in vitro growth of U87MG/Δ was resistant to Herstatin. Inhibition of U87MG growth correlated with suppressed EGF activation of EGFR and of Akt but not mitogen-activated protein kinase signaling pathways, whereas ΔEGFR activity and intracellular signaling in U87MG/Δ were unaffected by Herstatin treatment. Conclusions: Herstatin may have utility against glioblastoma driven by the EGFR but not the mutant ΔEGFR. Blockade of Akt but not the mitogen-activated protein kinase signaling cascade appears to be critical for suppression of intracranial tumor growth.

Original languageEnglish (US)
Pages (from-to)335-340
Number of pages6
JournalClinical Cancer Research
Volume11
Issue number1
StatePublished - Jan 1 2005

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Glioblastoma
Epidermal Growth Factor Receptor
Growth
Mitogen-Activated Protein Kinases
Nude Rats
herstatin
Epidermal Growth Factor
Signal Transduction
Neoplasms
Research Design
In Vitro Techniques
Brain

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Herstatin, an autoinhibitor of the epidermal growth factor receptor family, blocks the intracranial growth of glioblastoma. / Staverosky, Julia; Muldoon, Leslie; Guo, Shuhua; Evans, Adam J.; Neuwelt, Edward; Clinton, Gail M.

In: Clinical Cancer Research, Vol. 11, No. 1, 01.01.2005, p. 335-340.

Research output: Contribution to journalArticle

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AU - Neuwelt, Edward

AU - Clinton, Gail M.

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