來自俄亥俄州立大學(xué)綜合癌癥中心（Comprehensive Cancer Center）,，Dana-Farber癌癥研究所的研究人員發(fā)現(xiàn)了晚期,，非激素依賴性前列腺癌如何能夠在沒有激素的情況下繼續(xù)生長的奧秘，這一研究成果公布在Cell雜志上,。
文章的第一作者和共同通訊作者是俄亥俄州立大學(xué)分子與細胞生物化學(xué)助理教授王前奔博士,，其早期畢業(yè)于首都醫(yī)科大學(xué)，2002年獲得馬里蘭大學(xué)醫(yī)學(xué)院博士學(xué)位,，曾獲得過Travel Award青年科學(xué)家獎等獎項,。
這項研究聚焦于雄激素受體，這種受體定位于前列腺和其它組織細胞的細胞核上,，雄激素能結(jié)合這些受體,，從而激活調(diào)控細胞生長的基因。
研究人員發(fā)現(xiàn)非雄激素依賴性前列腺癌癥患者中,，雄激素受體被重組,，調(diào)控一組參與各種晚期細胞分裂的基因，導(dǎo)致細胞快速生長,，并且研究還表明染色體的一種主要成分的修改導(dǎo)致了這種重組,。
王前奔博士表示，“一些晚期前列腺癌的腫瘤生長并不需要雄激素,，但是需要雄激素受體”,，“我們的研究揭示了在非激素依賴性前列腺癌中雄激素受體的作用，以及這些受體如何在這種疾病中被激活,，和調(diào)控哪些基因促進腫瘤生長的,。”
前列腺癌是目前男性中最常見的癌癥之一，據(jù)估計2009年美國新出現(xiàn)的病例高達192280例，其中27360例死亡,。這項研究有利于進一步了解前列腺癌,，并且有助于新治療靶標的發(fā)現(xiàn)，從而為這種疾病的致命性階段提出新的治療方案,。
王前奔博士與Dana-Farber癌癥研究所的Myles Brown教授等人首先從激素依賴性和非激素依賴性前列腺癌細胞系,，基因表達數(shù)據(jù)，以及人類腫瘤組織等方面入手,，他們發(fā)現(xiàn)激素依賴性疾病中,，雄激素受體調(diào)控細胞周期的早期階段，但是在非激素依賴性前列腺癌中,，這些受體被重組,，選擇性調(diào)控細胞分裂中的基因，而細胞分裂正是有絲分裂細胞周期的晚期活動,。
這些基因中有一個名為“UBE2C”的基因受到了研究人員的關(guān)注,，他們發(fā)現(xiàn)這一基因的表達增加與非激素依賴性階段的生長密切相關(guān)，而且研究人員還發(fā)現(xiàn)這一基因相關(guān)的一個組蛋白上的表觀遺傳學(xué)變化能幫助雄激素受體結(jié)合并激活這一基因（非激素依賴性前列腺癌）,。除此之外,，非激素依賴性前列腺癌細胞的生長也需要UBE2C基因的過量表達。
王前奔博士說,，“有趣的是UBE2C基因在乳腺癌,，肺癌，卵巢癌,，膀胱癌,，甲狀腺癌和食道癌中也會表達過量，這說明我們的發(fā)現(xiàn)也許具有更廣泛的意義,。”（生物谷Bioon.com）
生物谷推薦原始出處：
Cell, Volume 138, Issue 2, 245-256, 23 July 2009 doi:10.1016/j.cell.2009.04.056
Androgen Receptor Regulates a Distinct Transcription Program in Androgen-Independent Prostate Cancer
Qianben Wang1,2,14,,,Wei Li3,14,Yong Zhang4,Xin Yuan5,Kexin Xu1,Jindan Yu6,Zhong Chen2,Rameen Beroukhim1,7,Hongyun Wang5,Mathieu Lupien1,13,Tao Wu8,Meredith M. Regan4,Clifford A. Meyer4,Jason S. Carroll9,Arjun Kumar Manrai4,Olli A. J?nne10,Steven P. Balk5,Rohit Mehra6,Bo Han6,Arul M. Chinnaiyan6,Mark A. Rubin11,Lawrence True12,Michelangelo Fiorentino1,Christopher Fiore1,Massimo Loda1,Philip W. Kantoff1,X. Shirley Liu4,,andMyles Brown1,,
1 Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA
2 Department of Molecular and Cellular Biochemistry and the Comprehensive Cancer Center, Ohio State University College of Medicine, Columbus, OH 43210, USA
3 Division of Biostatistics, Dan L. Duncan Cancer Center and Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA
4 Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute and Harvard School of Public Health, Boston, MA 02115, USA
5 Cancer Biology Program, Hematology-Oncology Division, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA
6 Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
7 Broad Institute of Harvard and MIT, Cambridge, MA 02139, USA
8 Department of System Biology, Harvard Medical School, Boston, MA 02115, USA
9 Cancer Research UK, Cambridge Research Institute, Robinson Way, Cambridge CB2 0RE, UK
10 Biomedicum Helsinki, Institute of Biomedicine (Physiology), University of Helsinki, Helsinki, FI-00014, Finland
11 Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY 10021, USA
12 Department of Pathology, University of Washington Medical Center, Seattle, WA 98195, USA
The evolution of prostate cancer from an androgen-dependent state to one that is androgen-independent marks its lethal progression. The androgen receptor (AR) is essential in both, though its function in androgen-independent cancers is poorly understood. We have defined the direct AR-dependent target genes in both androgen-dependent and -independent cancer cells by generating AR-dependent gene expression profiles and AR cistromes. In contrast to what is found in androgen-dependent cells, AR selectively upregulates M-phase cell-cycle genes in androgen-independent cells, including UBE2C, a gene that inactivates the M-phase checkpoint. We find that epigenetic marks at the UBE2C enhancer, notably histone H3K4 methylation and FoxA1 transcription factor binding, are present in androgen-independent cells and direct AR-enhancer binding and UBE2C activation. Thus, the role of AR in androgen-independent cancer cells is not to direct the androgen-dependent gene expression program without androgen, but rather to execute a distinct program resulting in androgen-independent growth.
