封面專題•COVER STORY 澳大新語•2020 UMAGAZINE 22 21 在癌細胞中，雄激素與其受體結合，這 些受體作為可調節基因表達的DNA結合 轉錄因子，能夠「啟動」基因而令前列 腺癌細胞生長及分裂。「與正常細胞不 同，前列腺癌細胞生長不受控制，因此 要瞭解前列腺癌的基因表達如何運作。」 研究人員過去不清楚雄激素受體如何與 基因結合，以控制前列腺癌細胞中基因 表達。張教授與來自美國、新加坡和內 地的研究人員首創性發現，在基因組三 維結構下，許多雄激素受體和基因的結 合點其實距離前列腺癌的基因很遠，意 味著雄激素受體能與遠處的基因發揮相 互作用，這發現改變了科學界在這研究 領域的認知。「研究人員過去不太清楚 lncRNA在前列腺癌細胞的作用。我們這 項研究提出，雄激素受體可能會在轉錄 過程中將lncRNA募集到靶向基因，因此 在基因表達中起著不可或缺的作用。」 張教授表示，目前有很多針對雄激素受 體的前列腺癌靶向藥物，但這些藥物未 必適合所有患者，尤其是復發患者。他 建議只有更加瞭解前列腺癌細胞的基因 表達，才有可能為每個患者找到合適治 療方法。「因此，我們下一個目標是找 出其它與前列腺癌細胞的基因表達有關 的因素，從而改善前列腺癌的治療。」 In cancer cells, androgens bind to AR, which acts as DNA-binding transcription factors that regulate gene expression and ‘turn on genes’ to make prostate cancer cells grow and divide. ‘However, unlike in normal cells, cell growth in prostate cancer cells is not properly controlled. So, it is important to understand how gene expression works,’ Prof Cheung says. Prof Cheung has been working with researchers from the United States, Singapore, and mainland China, in order to find out how AR and genes come together to start gene expression in prostate cancer cells. In a recent research paper, they point out that in the 3D structure of genome, many AR binding sites are far from the genes, which means that AR could interact with distant genes. In fact, Prof Cheung’s team was among the first to provide strong evidence for this discovery, which has changed the scientific community’s understanding of this field of research. ‘Besides, the role of long non-coding RNA (lncRNA) in prostate cancer cells was unclear to researchers in the past. Following this research, we suggested that the lncRNA can potentially be recruited by AR to target genes during transcription, thus playing an indispensable role in gene expression,’ he says. While there are existing drugs that treat prostate cancer by targeting AR, they may not be suitable for all patients, especially those with relapsed prostate cancer. Prof Cheung believes that only by better understanding the gene expression of prostate cancer cells will it be possible to find a suitable treatment for every patient. ‘Therefore, our next goal is to find out what other factors are involved in the gene expression of prostate cancer cells in order to improve the treatment of prostate cancer,’ says Prof Cheung. 張仲榮教授主要研究核內荷爾蒙訊號傳導及其與癌症等疾病的關係。曾在美國康奈爾大學擔任博士後研究員、 在新加坡基因組研究所擔任高級研究員。目前是《分子癌症研究》的編輯委員會成員。 Prof Edwin Cheung Chong Wing’s study focuses on intracellular hormone signalling and its relationship with cancer and other diseases. He was a postdoctoral research fellow at Cornell University and a senior investigator at the Genome Institute of Singapore. He is a member of the editorial board of Molecular Cancer Research. 核受體調節癌細胞中的轉錄過程 This picture shows how nuclear receptors regulate transcription in cancer cells
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