Department of Urology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania, United States of America.
PLoS One. 2011 May 6;6(5):e19771. doi: 10.1371/journal.pone.0019771.
MITOSTATIN, a novel putative tumor suppressor gene induced by decorin overexpression, is expressed in most normal human tissues but is markedly down-regulated in advanced stages of mammary and bladder carcinomas. Mitostatin negatively affects cell growth, induces cell death and regulates the expression and activation levels of Hsp27. In this study, we demonstrated that ectopic expression of Mitostatin in PC3, DU145, and LNCaP prostate cancer cells not only induced a significant reduction in cell growth, but also inhibited migration and invasion. Moreover, Mitostatin inhibited colony formation in soft-agar of PC3 and LNCaP cells as well as tumorigenicity of LNCaP cells in nude mice. Conversely, targeting endogenous Mitostatin by siRNA and anti-sense strategies in PC3 and DU145 prostate cancer cells enhanced the malignant phenotype in both cell lines. In agreement of these anti-oncogenic roles, we discovered that Mitostatin was absent in ∼35% (n = 124) of prostate tumor samples and its overall reduction was associated with advanced cancer stages. Collectively, our findings indicate that MITOSTATIN may acts as a tumor suppressor gene in prostate cancer and provide a novel cellular and molecular mechanism to be further exploited and deciphered in our understanding of prostate cancer progression.
抑瘤素 M，一种新的假定肿瘤抑制基因，由 decorin 过表达诱导，在大多数正常人类组织中表达，但在乳腺和膀胱癌的晚期明显下调。抑瘤素 M 负向影响细胞生长，诱导细胞死亡，并调节 Hsp27 的表达和激活水平。在这项研究中，我们证明了 Mitostatin 在 PC3、DU145 和 LNCaP 前列腺癌细胞中的异位表达不仅显著降低了细胞生长，还抑制了迁移和侵袭。此外，Mitostatin 抑制了 PC3 和 LNCaP 细胞在软琼脂中的集落形成以及 LNCaP 细胞在裸鼠中的致瘤性。相反，通过 siRNA 和反义策略靶向 PC3 和 DU145 前列腺癌细胞中的内源性 Mitostatin 增强了这两个细胞系的恶性表型。与这些抗肿瘤作用一致，我们发现 Mitostatin 在约 35%（n=124）的前列腺肿瘤样本中缺失，其总体减少与癌症晚期有关。总之，我们的发现表明 MITOSTATIN 可能在前列腺癌中作为肿瘤抑制基因发挥作用，并为进一步探索和破译我们对前列腺癌进展的理解提供了新的细胞和分子机制。
