IGF-1 receptor inhibition by picropodophyllin in medulloblastoma
| Autor: | Laura D. Nelon, Charles Keller, Tohru Hosoyama, Sachiko Ohshima-Hosoyama |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Biophysics
Biology Biochemistry Receptor IGF Type 1 Mice Downregulation and upregulation medicine Animals Humans Cerebellar Neoplasms Receptor Molecular Biology Cell Proliferation Podophyllotoxin Insulin-like growth factor 1 receptor Medulloblastoma Caspase 3 Cell growth Cell Biology medicine.disease Disease Models Animal Tumor progression Gene Knockdown Techniques Cancer research Picropodophyllin Tyrosine kinase |
| Zdroj: | Biochemical and Biophysical Research Communications. 399:727-732 |
| ISSN: | 0006-291X |
| DOI: | 10.1016/j.bbrc.2010.08.009 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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