Abstract | HYPOTHESIS: BACKGROUND: Recent evidence has implicated increased ErbB family receptor tyrosine kinase signaling in VS tumorigenesis; however, the characterization of ErbB receptor activity and the chemotherapeutic potential of RTK inhibitors in VS treatment have not been fully explored. METHODS: RESULTS: VS tumor tissues consistently demonstrated higher levels of phosphorylated ErbB3 compared with paired vestibular nerves. However, cultured VS, malignant schwannoma, and normal Schwann cells demonstrated EGFR phosphorylation. Immunohistochemistry confirmed high expression of ErbB3 in a series of VS tumor sections. Erlotinib inhibited schwannoma cell proliferation with an IC50 value of 2.5 µmol/L, whereas Lapatinib was less potent for growth inhibition. Erlotinib treatment resulted in a decrease of multiple phospho- ErbB receptors in schwannoma cells. CONCLUSION: VS variably express activated ErbB receptors with consistently higher levels of phospho-ErbB3 expression relative to paired vestibular nerve samples. Chemotherapeutic targeting of ErbB3 may be a novel means of inhibiting VS growth.
|
Authors | Matthew L Bush, Sarah S Burns, Janet Oblinger, Sholpan Davletova, Long-Sheng Chang, D Bradley Welling, Abraham Jacob |
Journal | Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology
(Otol Neurotol)
Vol. 33
Issue 2
Pg. 244-57
(Feb 2012)
ISSN: 1537-4505 [Electronic] United States |
PMID | 22222570
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
|
Chemical References |
- Antibodies, Monoclonal
- Antineoplastic Agents
- Oncogene Proteins v-erbB
- Quinazolines
- Lapatinib
- Erlotinib Hydrochloride
- Protein-Tyrosine Kinases
|
Topics |
- Antibodies, Monoclonal
(therapeutic use)
- Antineoplastic Agents
(pharmacology, therapeutic use)
- Blotting, Western
- Cell Line, Tumor
- Cell Proliferation
(drug effects)
- Ear Neoplasms
(drug therapy, pathology)
- Erlotinib Hydrochloride
- Humans
- Immunohistochemistry
- Lapatinib
- Neuroma, Acoustic
(drug therapy, pathology)
- Oncogene Proteins v-erbB
(antagonists & inhibitors)
- Phosphorylation
- Protein-Tyrosine Kinases
(genetics, metabolism)
- Quinazolines
(pharmacology, therapeutic use)
- Vestibular Nerve
(pathology)
|