State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, Shaanxi Province, China.
Cancer Biol Ther. 2010 Jan;9(2):88-95. doi: 10.4161/cbt.9.2.10283. Epub 2010 Jan 9.
Gankyrin, a small and highly conserved protein which is identical to the p28 gene product, was found to be related with the malignant phenotypes in liver and esophageal carcinoma. However, the roles of gankyrin in colorectal carcinoma (CRC) are still unknown. In the present study, the gankyrin mRNA and protein expression in human CRC cell lines and clinical tissue samples were evaluated and correlated with clinicopathological features. Possible mechanisms by which gankyrin regulates the malignant phenotype of CRC cells were also investigated. The results demonstrated that gankyrin was obviously overexpressed in CRC tissues and cell lines compared to controls, and gankyrin expression was correlated with TNM stages and metastasis of CRC. Overexpression of gankyrin by PhkitNeo-hGankyrin plasmid transfected into Lovo cells could promote the cell proliferation and tumorigenicity. This finding was further strengthened by experiments that suppressing gankyrin expression by siRNA exerted the opposite effects on CRC cells SW620. In addition, our present study showed that the co-expression of cyclinD1 and beta-catenin were positive correlation with the alteration of gankyrin expression. This data suggested that gankyrin played significant roles in the pathogenesis of human CRC, and might be an important therapeutic target for CRC.
Gankyrin 是一种小型且高度保守的蛋白，与 p28 基因产物相同，被发现与肝癌和食管癌的恶性表型有关。然而，Gankyrin 在结直肠癌（CRC）中的作用仍不清楚。在本研究中，评估了 Gankyrin 在人 CRC 细胞系和临床组织样本中的 mRNA 和蛋白表达，并与临床病理特征相关。还研究了 Gankyrin 调节 CRC 细胞恶性表型的可能机制。结果表明，与对照组相比，Gankyrin 在 CRC 组织和细胞系中明显过表达，Gankyrin 的表达与 CRC 的 TNM 分期和转移相关。通过 PhkitNeo-hGankyrin 质粒转染到 Lovo 细胞中过表达 Gankyrin 可以促进细胞增殖和致瘤性。通过实验进一步证实了这一发现，即用 siRNA 抑制 Gankyrin 的表达对 CRC 细胞 SW620 产生了相反的效果。此外，本研究表明，cyclinD1 和 β-catenin 的共表达与 Gankyrin 表达的改变呈正相关。这些数据表明，Gankyrin 在人类 CRC 的发病机制中起重要作用，可能是 CRC 的一个重要治疗靶点。
