来自俄亥俄州立大学综合癌症中心（Comprehensive Cancer Center）和Dana-Farber癌症研究所的研究人员，发现了晚期非激素依赖性前列腺癌如何在缺乏雄激素的情况下继续生长的分子机制。这一成果于2009年7月23日发表在《Cell》杂志上。
文章的第一作者和共同通讯作者是俄亥俄州立大学分子与细胞生物化学助理教授王前奔博士。他早年毕业于首都医科大学，2002年获得马里兰大学医学院博士学位，曾获得Travel Award青年科学家奖等荣誉。
本研究聚焦于雄激素受体（AR），该受体定位于前列腺及其他组织细胞的细胞核上。雄激素与受体结合后，激活调控细胞生长的基因。在非激素依赖性前列腺癌中，雄激素受体被重组，转而调控一组参与有丝分裂后期细胞分裂的基因，导致细胞快速增殖。研究还发现，染色体的一种主要成分——组蛋白的修饰导致了这种重组。
王前奔博士表示：“一些晚期前列腺癌的肿瘤生长并不需要雄激素，但需要雄激素受体。我们的研究揭示了非激素依赖性前列腺癌中雄激素受体的作用机制，以及这些受体如何被激活并调控促进肿瘤生长的基因。”
前列腺癌是男性中最常见的癌症之一。据估计，2009年美国新发病例高达192,280例，其中27,360例死亡。这项研究不仅加深了对前列腺癌的理解，还有助于发现新的治疗靶点，为疾病的致命阶段提供新的治疗方案。
王前奔博士与Dana-Farber癌症研究所的Myles Brown教授等人，首先从激素依赖性和非激素依赖性前列腺癌细胞系、基因表达数据以及人类肿瘤组织入手。他们发现，在激素依赖性疾病中，雄激素受体调控细胞周期的早期阶段；但在非激素依赖性前列腺癌中，这些受体被重组，选择性调控细胞分裂中的基因，而细胞分裂正是有丝分裂细胞周期的晚期活动。
在这些基因中，一个名为UBE2C的基因引起了研究人员的关注。他们发现，UBE2C基因的表达增加与非激素依赖性阶段的生长密切相关。进一步研究表明，该基因相关的一个组蛋白上的表观遗传学变化，帮助雄激素受体结合并激活该基因。此外，非激素依赖性前列腺癌细胞的生长也需要UBE2C基因的过量表达。
王前奔博士指出：“有趣的是，UBE2C基因在乳腺癌、肺癌、卵巢癌、膀胱癌、甲状腺癌和食管癌中也会过量表达，这表明我们的发现可能具有更广泛的意义。”
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 Wang, Wei Li, Yong Zhang, Xin Yuan, Kexin Xu, Jindan Yu, Zhong Chen, Rameen Beroukhim, Hongyun Wang, Mathieu Lupien, Tao Wu, Meredith M. Regan, Clifford A. Meyer, Jason S. Carroll, Arjun Kumar Manrai, Olli A. Jänne, Steven P. Balk, Rohit Mehra, Bo Han, Arul M. Chinnaiyan, Mark A. Rubin, Lawrence True, Michelangelo Fiorentino, Christopher Fiore, Massimo Loda, Philip W. Kantoff, X. Shirley Liu, and Myles Brown
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.