Vanli Nil, Guo-Fu H U
Molecular Oncology Research Institute, Tufts Medical Center Graduate Program in Biochemistry, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, MA 02111, USA.
Zhongguo Sheng Wu Hua Xue Yu Fen Zi Sheng Wu Xue Bao. 2015 Dec 20;31(12):1261-1266. doi: 10.13865/j.cnki.cjbmb.2015.12.06. Epub 2015 Dec 24.
Angiogenin (ANG), the fifth member of the vertebrate-specific ribonuclease (RNase) A superfamily, is a secreted angiogenic ribonuclease strongly up-regulated in human prostate cancers. ANG is translocated to the nucleus in both prostate cancer epithelial cells and endothelial cells to exert its role in prostate cancer progression by mediating tumor angiogenesis, cancer cell survival and proliferation through rRNA biogenesis. ANG-stimulated rRNA is required not only for prostate intraepithelial neoplasia (PIN) formation, but also for androgen-independent growth of prostate cancer cells. Targeting ANG by various antagonists that inhibit its nuclear translocation, function and/or activity has proven to inhibit prostate cancer growth in animal models. Furthermore, the role of ANG in androgen independence has been firmly established, suggesting a strong rationale for therapeutically targeting ANG in the treatment of castration resistant prostate cancer.
血管生成素(ANG)是脊椎动物特有的核糖核酸酶(RNase)A超家族的第五个成员,是一种分泌型血管生成核糖核酸酶,在人类前列腺癌中强烈上调。ANG在前列腺癌上皮细胞和内皮细胞中均易位至细胞核,通过rRNA生物合成介导肿瘤血管生成、癌细胞存活和增殖,从而在前列腺癌进展中发挥作用。ANG刺激的rRNA不仅是前列腺上皮内瘤变(PIN)形成所必需的,也是前列腺癌细胞雄激素非依赖性生长所必需的。通过各种抑制其核转位、功能和/或活性的拮抗剂靶向ANG,已被证明在动物模型中可抑制前列腺癌生长。此外,ANG在雄激素非依赖性中的作用已得到确证,这为在去势抵抗性前列腺癌治疗中靶向ANG提供了强有力理据。