Overexpression of a novel gene gankyrin correlates with the malignant phenotype of colorectal cancer

• Published in: Cancer biology & therapy 2010-01, Vol.9 (2), p.88-95
• Main Authors: Tang, Shanhong, Yang, Guitao, Meng, Yun, Du, Rui, Li, Xiaohua, Fan, Rui, Zhao, Lina, Bi, Qian, Jin, Jiang, Gao, Liucun, Zhang, Lin, Li, Hao, Fan, Meng, Wang, Yingmei, Wu, Kaichun, Liu, Jie, Fan, Daiming
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - genetics; Adenocarcinoma - pathology; Aged; Animals; Binding; Biology; Bioscience; Blotting, Western; Calcium; Cancer; Cell; Cell Differentiation; Cell Line, Transformed - metabolism; Cell Line, Transformed - transplantation; Colorectal Neoplasms - genetics; Colorectal Neoplasms - pathology; Cycle; Female; Gene Expression Regulation, Neoplastic; Humans; Immunoenzyme Techniques; Landes; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Middle Aged; Neoplasm Proteins - biosynthesis; Neoplasm Proteins - genetics; Neoplasm Proteins - physiology; Neoplasm Staging; Neoplasm Transplantation; Organogenesis; Polymerase Chain Reaction; Proteasome Endopeptidase Complex - biosynthesis; Proteasome Endopeptidase Complex - genetics; Proteasome Endopeptidase Complex - physiology; Proteins; Proto-Oncogene Proteins - biosynthesis; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - physiology; Recombinant Fusion Proteins - biosynthesis; RNA Interference; RNA, Messenger - biosynthesis; RNA, Neoplasm - biosynthesis; RNA, Small Interfering - pharmacology; Transfection
• ISSN: 1538-4047; 1555-8576
• DOI: 10.4161/cbt.9.2.10283

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 β-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.