ErbB and Nrg: potential molecular targets for vestibular schwannoma pharmacotherapy

Otology & Neurotology : Official Publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology
Joni K DohertyAllen F Ryan

Abstract

Identify molecular targets for development of tumor-specific pharmacotherapeutics aimed at treating vestibular schwannomas (VSs). Activated epidermal growth factor receptor B (ErbB) 2 and ErbB3 are abundantly expressed in VS. ErbB2 signaling is essential for Schwann cell differentiation, survival, and proliferation. VS arise after loss of functional merlin, a putative tumor suppressor. Merlin internalizes ErbB2 receptors in rodent Schwann cells. Unregulated ErbB signaling may contribute to VS tumorigenesis. Molecular analyses, retrospective clinical correlation. Tertiary referral center. Thirty-eight specimens from patients operated for sporadic (n=21) and neurofibromatosis (NF) 2-related (n=17) VS. VS analyses via real-time polymerase chain reaction, immunohistochemistry, and correlation with patient clinical data. ErbB signaling molecule expression, tumor size, age, and NF2 status. VS upregulated epidermal growth factor (EGF) receptor in 68% (62% sporadic and 75% NF2-associated VS) and ErbB2 in 84% (76% sporadic and 94% NF2-related VS). ErbB3 was upregulated in 34%, and ErbB4 is downregulated in NF2-related VS. Of EGF receptor (EGFR) ligands, EGF was upregulated in all NF2-related VS, but none of the sporadic VS (p<0.01), and...Continue Reading

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Jun 11, 2011·Otology & Neurotology : Official Publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology·Zana K AhmadJoni K Doherty
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