Adenovirus-mediated transfer of FRNK augments drug-induced cytotoxicity in cultured SCCHN cells.
BACKGROUND
Focal adhesion kinase (FAK), which is overexpressed in many human epithelial cancers, regulates cell cycle progression, cellular migration, invasion and survival.


METHODS
In order to determine if inhibiting FAK activity augments drug-induced cytotoxicity in transformed epithelial cells from the head and neck region (SCCHN cells), cells were transfected with a recombinant adenovirus causing overexpression of FRNK a dominant negative inhibitor of FAK Results: When SCCHN cells (SCC25 and RPMI 2650) were transfected with Ad-FRNK there was a decrease in autophosphorylation of FAK, coincident with a large increase in FRNK expression. Ad-FRNK and cytotoxic drugs were more effective in reducing cell viability and increasing apoptosis then Ad-FRNK alone or drugs alone. Transfection with Ad-FRNK also led to substantially decreased migration of cultured SCCHN cells. These results indicate that FAK may be a good target for anticancer therapy.
Kornberg
Lori J
LJ
Department of Otolaryngology, University of Florida College of Medicine, Gainesville, Florida 32610, USA. kornblj@ent.ufl.edu
D000256:Adenoviridae / Q000235:genetics / Q000502:physiology*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics / Q000628:therapy*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D003131:Combined Modality Therapy; D005047:Etoposide / Q000494:pharmacology; D005472:Fluorouracil / Q000494:pharmacology; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D015316:Genetic Therapy / Q000379:methods; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics / Q000628:therapy*; D006801:Humans; D017239:Paclitaxel / Q000494:pharmacology; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D014162:Transfection
D005047:Etoposide; C113183:FAK-related nonkinase; D011505:Protein-Tyrosine Kinases; D051416:Focal Adhesion Protein-Tyrosine Kinases; D017239:Paclitaxel; D005472:Fluorouracil