金屬硫蛋白（MT）是個富含半胱氨酸的低分子量蛋白質，與金屬具有極高的親和力。MT藉由金屬感應轉錄因子（MTF-1）調控其表現；其中鋅及鎘都可以刺激MTF-1的活化，促進MT基因的表現。先前的研究證實，在人類或老鼠細胞中，鋅可以增加Src的磷酸化，增加細胞內Src的活性。在本篇的研究中，我們研究鋅所誘導Src的活化對MT基因表現的影響。在HEK293細胞中給予鋅的刺激，Src磷酸化的程度，會隨著鋅的劑量增加；另一方面，Src磷酸化的程度，在處理2個小時達到最大值，4個小時便回復至沒有處理時的情況。細胞給予鎘的刺激，對於Src的磷酸化，則沒有影響。處理Src抑制劑（PP2）或Src siRNA，再給予鋅的刺激，都會導致MT基因的表現更增加。我們更進一步證實，鋅活化Src後，會藉由磷酸化EGFR活化下游的Ras/Raf/MEK/ERK訊號傳遞路徑；處理EGFR siRNA 、Ras、Raf或MEK抑制劑（Manumycin A、Bay43-9006、PD98059），再給予鋅的刺激，也都會導致MT基因的表現更增加。最後，活化的ERK會增加IKK磷酸化，間接活化NF-κB；處理Src或MEK抑制劑，則都可以抑制NF-κB的活化。我們的研究結果證實，鋅誘導Src的活化，扮演一個抑制MT基因表現的角色。

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