Wang Hongyun, Leav Irwin, Ibaragi Soichiro, Wegner Michael, Hu Guo-fu, Lu Michael L, Balk Steven P, Yuan Xin
Cancer Biology Program, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Cancer Res. 2008 Mar 15;68(6):1625-30. doi: 10.1158/0008-5472.CAN-07-5915.
SOX9 is a transcription factor that plays a critical role in the development of multiple tissues. We previously reported that SOX9 in normal human adult prostate was restricted to basal epithelium. SOX9 was also expressed in a subset of prostate cancer (PCa) cells and was increased in relapsed hormone-refractory PCa. Moreover, SOX9 expression in PCa cell lines enhanced tumor cell proliferation and was beta-catenin regulated. Here we report additional in vivo results showing that SOX9 is highly expressed during fetal prostate development by epithelial cells expanding into the mesenchyme, suggesting it may contribute to invasive growth in PCa. Indeed, SOX9 overexpression in LNCaP PCa xenografts enhanced growth, angiogenesis, and invasion. Conversely, short hairpin RNA-mediated SOX9 suppression inhibited the growth of CWR22Rv1 PCa xenografts. These results support important functions of SOX9 in both the development and maintenance of normal prostate, and indicate that these functions contribute to PCa tumor growth and invasion.
SOX9是一种转录因子，在多种组织的发育中起关键作用。我们之前报道过，正常成年男性前列腺中的SOX9局限于基底上皮。SOX9也在一部分前列腺癌细胞（PCa）中表达，且在复发的激素难治性PCa中表达增加。此外，PCa细胞系中SOX9的表达增强了肿瘤细胞增殖，且受β-连环蛋白调控。在此我们报告更多体内实验结果，显示在胎儿前列腺发育过程中，SOX9在上皮细胞向间充质扩展时高表达，提示其可能促进PCa的侵袭性生长。事实上，LNCaP PCa异种移植瘤中SOX9的过表达增强了生长、血管生成和侵袭。相反，短发夹RNA介导的SOX9抑制抑制了CWR22Rv1 PCa异种移植瘤的生长。这些结果支持了SOX9在正常前列腺发育和维持中的重要功能，并表明这些功能促进了PCa肿瘤的生长和侵袭。
