據(jù)香港文匯報報道，肝癌為香港最常見的癌癥,，男性發(fā)病率更較女性高出3倍,，惟個中原理一直為未解之謎,。香港中文大學以3年時間研究,，發(fā)現(xiàn)男性荷爾蒙能誘發(fā)一種導致肝癌的基因“CCRK”,，令肝臟細胞異常快速繁殖,，促成腫瘤的形成,，完整解釋男性較易患肝癌的原因。
研究又發(fā)現(xiàn),，70%肝癌病人“CCRK”高于正常水平,，若降低“CCRK”或阻礙其分子信息通路，能有效減慢腫瘤生長,。中大校長沈祖堯表示,，“CCRK”很可能為治癌標靶，今次發(fā)現(xiàn)有助開發(fā)新藥造福病人,。
肝癌男性發(fā)病率較女性高的謎團終被解開,。中大醫(yī)學院消化疾病研究所由2008年起，以基因組定位技術及生物信息學分析,，從逾17,000個人類基因中,，找出一個名為“細胞周期相關性激素”(CCRK)的基因，并證實其與男性荷爾蒙受體,，以及肝癌有密切關系,。
消化疾病研究所研究副教授鄭詩樂表示，男士如患有乙型肝炎,，其男性荷爾蒙受體會被激活,，與男性荷爾蒙結合后，會入侵肝細胞的細胞核,，啟動并增加“CCRK”的含量,，繼而引發(fā)一連串名為分子信息通路的化學反應，激發(fā)細胞異?？焖俜敝?，并轉化形成腫瘤細胞，導致肝癌的發(fā)生,。
研究所為逾50名肝癌病人驗測,，發(fā)現(xiàn)70%患者的“CCRK”遠高于正常水平，而“CCRK”高的肝癌病人較多為末期患者,，其術后存活率3年已大跌50%,，反之“CCRK”低的患者，6年存活率仍達100%,。小鼠實驗更進一步證實,，降低肝癌細胞“CCRK”的含量,，以及阻礙“CCRK”分子信息通路，均能有效減慢腫瘤形成的速度,。
研究主管兼莫慶堯醫(yī)學講座教授沈祖堯解釋,，每個人體內也有“CCRK”基因，但含量高低各有不同,，醫(yī)學界過去只知“CCRK”對腦部有一定作用,，今次研究則首次發(fā)現(xiàn)“CCRK”對肝臟有所反應，“荷爾蒙會喚醒沉睡的基因,，令不正常細胞快速增長”,。
中大下一步會把“CCRK”與小鼠自身基因結合，讓小鼠從出世已帶有“CCRK”,，看其會否發(fā)展成為肝癌,，亦會研究針對“CCRK”的標靶治療，冀能開發(fā)肝癌新標靶藥物,。有關研究結果已刊載于權威生物醫(yī)學刊物《臨床調查雜志》7月份網(wǎng)上版,。(生物谷 Bioon.com)
生物谷推薦原文出處：
The Journal Of Clinical Investigation doi:10.1172/JCI45967.
Cell cycle–related kinase is a direct androgen receptor–regulated gene that drives β-catenin/T cell factor–dependent hepatocarcinogenesis
Hai Feng, Alfred S.L. Cheng, Daisy P. Tsang, May S. Li, Minnie Y. Go, Yue S. Cheung, Gui-jun Zhao, Samuel S. Ng, Marie C. Lin, Jun Yu1,, Paul B. Lai, Ka F. To and Joseph J.Y. Sung
Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. It is more prevalent in men than women. Related to this, recent genetic studies have revealed a causal role for androgen receptor (AR) in hepatocarcinogenesis, but the underlying molecular mechanism remains unclear. Here, we used genome-wide location and functional analyses to identify a critical mediator of AR signaling — cell cycle–related kinase (CCRK) — that drives hepatocarcinogenesis via a signaling pathway dependent on β-catenin and T cell factor (TCF). Ligand-bound AR activated CCRK transcription and protein expression via direct binding to the androgen-responsive element of the CCRK promoter in human HCC cell lines. In vitro analyses showed that CCRK was critical in human cell lines for AR-induced cell cycle progression, hepatocellular proliferation, and malignant transformation. Ectopic expression of CCRK in immortalized human liver cells activated β-catenin/TCF signaling to stimulate cell cycle progression and to induce tumor formation, as shown in both xenograft and orthotopic models. Conversely, knockdown of CCRK decreased HCC cell growth, and this could be rescued by constitutively active β-catenin or TCF. In primary human HCC tissue samples, AR, CCRK, and β-catenin were concordantly overexpressed in the tumor cells. Furthermore, CCRK overexpression correlated with the tumor staging and poor overall survival of patients. Our results reveal a direct AR transcriptional target, CCRK, that promotes hepatocarcinogenesis through the upregulation of β-catenin/TCF signaling.
