Taxotere activates transcription factor AP-1 in association with apoptoticcell death in gastric cancer cell lines

We investigated whether a novel mitotic inhibitor; taxotere can activate th e transcription factor AP-1 in association with apoptotic cell death in 8 g astric cancer cell lines. Apototic cell death was analyzed by DNA ladder fo rmation assay, and AP-1 binding activity was assessed by gel mobility-shift assay. The activation of AP-1 binding was induced in accordance with the s ensitivity to taxotere in gastric cancer cell lines. The relationship betwe en the increase of AP-I binding and the formation of internucleosomal DNA l adders induced by taxotere was significant (p<0.05). Further more, the acti vation of AP-1 binding was induced following the treatment of taxotere in a dose and -time dependent manner. Although the sensitivity to taxotere was correlated with the formation of internucleosomal DNA ladders in apoptotic cell death, its sensitivity was nor influenced by their p53 genomic states in gastric cancer cell lines. Rather, the activation of AP-1 binding was co rrelated with the induction of a growth nn-est and DNA damage inducible gen e, gadd153 (p<0.05). These results indicate that the activation of AP-1 bin ding by taxotere seems to be an important factor in determining its sensiti vity in association with internucleosomal DNA ladders, and suggest that the induction of gadd153 gene could be a downstream target of AP-1-regulated g enes involved in signal transduction pathways lending to apoptosis in gastr ic cancer cells.