Abstract |
Neuroblastoma is the most common extracranial solid tumor of childhood. Focal adhesion kinase (FAK) is an intracellular kinase that is overexpressed in a number of human tumors including neuroblastoma, and regulates both cellular adhesion and survival. We have studied the effects of FAK inhibition upon neuroblastoma using adenovirus-containing FAK-CD (AdFAK-CD). Utilizing an isogenic MYCN+/MYCN- neuroblastoma cell line, we found that the MYCN+ cells are more sensitive to FAK inhibition with AdFAK-CD than their MYCN negative counterparts. In addition, we have shown that phosphorylation of Src is increased in the untreated isogenic MYCN- neuroblastoma cells, and that the decreased sensitivity of the MYCN- neuroblastoma cells to FAK inhibition with AdFAK-CD is abrogated by the addition of the Src family kinase inhibitor, PP2. The results of the current study suggest that both FAK and Src play a role in protecting neuroblastoma cells from apoptosis, and that dual inhibition of these kinases may be important when designing therapeutic interventions for this tumor.
|
Authors | Elizabeth A Beierle, Xiaojie Ma, Angelica Trujillo, Elena V Kurenova, William G Cance, Vita M Golubovskaya |
Journal | Molecular carcinogenesis
(Mol Carcinog)
Vol. 49
Issue 3
Pg. 224-34
(Mar 2010)
ISSN: 1098-2744 [Electronic] United States |
PMID | 19885861
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
|
Copyright | (c) 2009 Wiley-Liss, Inc. |
Chemical References |
- PARP1 protein, human
- Poly (ADP-Ribose) Polymerase-1
- Poly(ADP-ribose) Polymerases
- Focal Adhesion Kinase 1
- PTK2 protein, human
- Proto-Oncogene Proteins pp60(c-src)
|
Topics |
- Adenoviridae
(genetics)
- Apoptosis
- Blotting, Western
- Cell Adhesion
- Cell Movement
- Cell Proliferation
- Flow Cytometry
- Focal Adhesion Kinase 1
(antagonists & inhibitors)
- Genes, myc
- Humans
- Neuroblastoma
(metabolism, pathology)
- Phosphorylation
- Poly (ADP-Ribose) Polymerase-1
- Poly(ADP-ribose) Polymerases
(metabolism)
- Proto-Oncogene Proteins pp60(c-src)
(antagonists & inhibitors)
- Tumor Cells, Cultured
|