Acetylation是Histone modification諸多型式中的一種，可以調控Gene transcription。而Histone acetylase (HAT)及Histone deacetylase(HDAC)則為兩個互為拮抗、調控細胞內Histoneacetylation的重要酵素。Trichostatin A (TSA)是一個Histone deacetylase (HDAC)的抑制劑。先前已有報導指出其可抑制多種致癌基因所引發的細胞癌化。本實驗室在研究v-Src細胞癌化的過程中，意外發現TSA可以抑制其生長、分裂。在進一步探究其作用機轉時，我們也觀察到TSA處理後的v-Src transformed cells，其p97/sup Eps8/的量有顯著下降。先前我們已指出eps8是一個致癌基因，且p97/sup Eps8/是Src substrate。故TSA有可能透過抑制p97/sup Eps8/的表現量而具有抑癌能力。 In order Histone acetylase (HAT) and histone deacetylase (HDAC) are two crucial enzymes determining the structure of chromatin that regulates gene expression. In this study, we observed that TSA, a specific HDAC inhibitor, could effectively inhibit the growth of v-Src transformed cells and abrogated their ability to form colonies in soft agar. By further dissecting the growth inhibition mechanisms, we found that while TSA could reduce the expression of Eps8, no alteration of Src expression and kinase activity was observed. Interestingly, removal of TSA could restore both the cellular growth and the expression of Eps8. Northern and RT-PCR analysis revealed the significant reduction of eps8 transcript in TSA-treated v-Src transformed cells relative to control. Since v-Src enhanced p97/sup Eps8/ expression and overexpression of p97/sup Eps8/ could lead to cellular transformation, thus the observed correlation between TSA-reduced p97/sup Eps8/ expression and TSA-induced growth inhibition of v-Src transformed cells implicated the involvement of p97/sup Eps8/ in v-Src-induced transformation. Indeed, expression of dominant negative p97/sup Eps8/ abolished the transformation caused by v-Src. Based on these findings, we conclude that p97/sup Eps8/ plays a crucial role in v-Src-induced transformation.
