Michigan Center for Translational Pathology, Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109-0602, USA.
Neoplasia. 2012 Oct;14(10):905-14. doi: 10.1593/neo.121192.
Transcriptional repressors and corepressors play a critical role in cellular homeostasis and are frequently altered in cancer. C-terminal binding protein 1 (CtBP1), a transcriptional corepressor that regulates the expression of tumor suppressors and genes involved in cell death, is known to play a role in multiple cancers. In this study, we observed the overexpression and mislocalization of CtBP1 in metastatic prostate cancer and demonstrated the functional significance of CtBP1 in prostate cancer progression. Transient and stable knockdown of CtBP1 in prostate cancer cells inhibited their proliferation and invasion. Expression profiling studies of prostate cancer cell lines revealed that multiple tumor suppressor genes are repressed by CtBP1. Furthermore, our studies indicate a role for CtBP1 in conferring radiation resistance to prostate cancer cell lines. In vivo studies using chicken chorioallantoic membrane assay, xenograft studies, and murine metastasis models suggested a role for CtBP1 in prostate tumor growth and metastasis. Taken together, our studies demonstrated that dysregulated expression of CtBP1 plays an important role in prostate cancer progression and may serve as a viable therapeutic target.
转录抑制剂和共抑制剂在细胞内稳态中起着至关重要的作用，并且经常在癌症中发生改变。C 端结合蛋白 1（CtBP1）是一种转录共抑制剂，可调节肿瘤抑制因子和参与细胞死亡的基因的表达，已知其在多种癌症中发挥作用。在这项研究中，我们观察到转移性前列腺癌中 CtBP1 的过度表达和定位错误，并证明了 CtBP1 在前列腺癌进展中的功能意义。在前列腺癌细胞中瞬时和稳定敲低 CtBP1 抑制了它们的增殖和侵袭。前列腺癌细胞系的表达谱研究表明，多种肿瘤抑制基因受 CtBP1 抑制。此外，我们的研究表明 CtBP1 在赋予前列腺癌细胞系辐射抗性方面发挥作用。鸡胚绒毛尿囊膜分析、异种移植研究和小鼠转移模型的体内研究表明，CtBP1 参与了前列腺肿瘤的生长和转移。综上所述，我们的研究表明，CtBP1 的失调表达在前列腺癌的进展中起着重要作用，并且可能成为一种可行的治疗靶标。
