OBJECTIVES/HYPOTHESIS: Both the @entity470 ( @entity470 ) and the @entity876 homologue @entity4206 are overexpressed in a significant number of cases of @entity213 ( @entity213 ). @entity470 and @entity4206 both possess oncogenic properties, including the potential to increase cell proliferation and antagonize apoptosis. @entity4562 ("Iressa") is an @entity855 -competitive inhibitor specific to the @entity470 @entity669 kinase currently under evaluation as a chemotherapeutic agent in @entity213 . The objective was to investigate whether @entity4206 expression is decreased after treatment of @entity213 cells with @entity4562 . Downregulation of @entity4206 by @entity4562 would identify a potential molecular relationship between @entity470 signaling and @entity4206 and could provide insight into the mechanism of action of @entity4562 . STUDY DESIGN: In vitro examination of @entity4206 expression after @entity4562 treatment. METHODS: A @entity1 @entity213 cell line, SCC-012, was treated with varying doses of @entity4562 . @entity4206 protein and messenger RNA levels were analyzed by Western and Northern blot analyses. The effect of @entity4562 on SCC-012 cell cycle was analyzed by flow cytometric analysis. RESULTS: In SCC-012 cells there was a dose-dependent decrease in @entity4206 protein and messenger RNA levels over the course of @entity4562 treatment. Levels of phosphorylated MAPK decreased and @entity13525 levels increased after @entity4562 treatment. @entity4562 treatment induced a twofold increase in G1-phase cells and a 3.5-fold decrease in S-phase cells consistent with @entity851 . CONCLUSION: @entity4562 downregulates @entity4206 expression at the messenger RNA level, suggesting that @entity4206 is a downstream target of @entity470 signaling.

Inhibition of @entity470 signaling decreases XXXX expression in head and neck squamous carcinoma cells.

@entity1 :: ('9606', 'Species') :: ['human'] @entity851 :: ('MESH:D006130', 'Disease') :: ['growth arrest'] @entity4562 :: ('MESH:C419708', 'Chemical') :: ['ZD1839'] @entity470 :: ('1956', 'Gene') :: ['Epidermal growth factor receptor', 'EGFR', 'epidermal growth factor receptor'] @entity4206 :: ('8626', 'Gene') :: ['p63'] @entity876 :: ('7157', 'Gene') :: ['p53'] @entity855 :: ('MESH:D000255', 'Chemical') :: ['adenosine triphosphate'] @entity13525 :: ('1027', 'Gene') :: ['p27KIP-1'] @entity669 :: ('CHEBI:18186', 'Chemical') :: ['tyrosine'] @entity213 :: ('MESH:C535575', 'Disease') :: ['head and neck squamous cell carcinoma', 'HNSCC']
@entity4206 :: (8626,Gene) :: ['p63']
