Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China.
J Exp Clin Cancer Res. 2012 Aug 21;31(1):67. doi: 10.1186/1756-9966-31-67.
LATS1 is a tumor suppressor genes implicated in the pathogenesis of certain types of tumors, but its role is not known in human glioma.
Using real-time PCR and immunohistochemistry, we detected the mRNA and protein expression of LATS1 in glioma. The effect of LATS1 on cell growth and invasion were investigated.
We found that mRNA and protein of LATS1 expression is significantly downregulated in glioma compared with normal control brain tissues. Furthermore, reduced LATS1 expression was markedly negatively correlated with WHO grade and KPS (p<0.001 and p<0.001) in glioma patients. Patients with lower LATS1 expression had a significantly shorter overall survival time than did patients with higher LATS1 expression. Multivariate analysis suggested that the level of LATS1 expression was an independent prognostic indicator (p<0.001) for the survival of patients with glioma. Forced expression of LATS1 in glioma U251 cells not only significantly suppressed cell growth, migration and invasion, but retarded cell cycle progression from G2/M to G1 in vitro. Finally, we found that overexpressed LATS1 markedly inhibited the expression level of cell cycle factor CCNA1.
These results indicate that LATS1 is an important candidate tumor suppressor and its downregulated expression may contribute to glioma progression.
LATS1 是一种肿瘤抑制基因，与某些类型肿瘤的发病机制有关，但在人类脑胶质瘤中的作用尚不清楚。
采用实时 PCR 和免疫组织化学方法检测 LATS1 在脑胶质瘤中的 mRNA 和蛋白表达。研究 LATS1 对细胞生长和侵袭的影响。
我们发现与正常对照脑组织相比，LATS1 的 mRNA 和蛋白表达在脑胶质瘤中明显下调。此外，LATS1 表达降低与脑胶质瘤患者的 WHO 分级和 KPS 呈显著负相关（p<0.001 和 p<0.001）。LATS1 表达较低的患者总生存时间明显短于 LATS1 表达较高的患者。多因素分析表明，LATS1 表达水平是脑胶质瘤患者生存的独立预后指标（p<0.001）。在体外，LATS1 在脑胶质瘤 U251 细胞中的过表达不仅显著抑制细胞生长、迁移和侵袭，而且还使细胞周期从 G2/M 向 G1 阻滞。最后，我们发现过表达的 LATS1 明显抑制了细胞周期因子 CCNA1 的表达水平。
这些结果表明，LATS1 是一种重要的候选肿瘤抑制基因，其下调表达可能有助于脑胶质瘤的进展。
