Frizzled Activation by Wnt-l Is Required for beta -Catenin -T Cell Factor Dependent Transcription in Esophageal Cancer

Although, accumulation of nuclear and cytoplasmic beta-catenin has been observed in ESCCs, mutation of APC and beta-catenin are not found in ESCCs. Therefore, another mechanism for cytoplasmic beta- catenin accumulation might exist in ESCCs. Materials and Methods: Human ESCCs cell lines and the 293 stable transfectants expressing Wnt-1, Wnt-5A, and Wnt-7A were cultured under standard conditions. The TOPFlash or FOPFlash reporter plasmids were transfected. Results: Transfected mutant beta-catenin as well as an axin fragment harbing the GSK3 beta interaction domain, the latter a potent GSK3 beta inhibitor. both robustly activated pTOPFlash in ESCCs cells. When pTOPFlash/pFOPFlash reporters were transfected in ESCCs cell lines followed by cocultivation with 293 cells that stably express Wnt -1, all cell lines except one demonstrated TCF mediated transcriptional. But, cells were co- cultured, Wnt - 7A or Wnt - 5A did not activate TCF mediated transcription in a cell number dependent fashion. Discussion; We report the activation of TCF promoter gene by extemal Wnt stimuli in ESCCs cells.

背景:食道癌細胞にベータカテニンの蓄積があることは報告されているが,大腸癌とことなり,ベータカテニン,Axin,APC変異の報告がなく,そのメカニズムは不明である｡ 方法:8種類の食道癌細胞株において,3種類のWntの刺激によるベータカテニンTCF系の活性化への影響をTCFプロモーターを持つルシュフフェラーゼプラスミドを癌細胞にトランスフェクションして検討した｡ 結果:代表的な食道癌細胞は変異ベータカテニン,変異APC,変異Axinのいずれも,TCFの活性化をおこした｡8種類中7種類の癌細胞はWnt1により量依存性のTCFの活性化が認められたが,Wnt5A,Wnt7Aでは活性化が認められなかった｡ 結語:食道癌の進展にWnt1の関与が示唆された｡