RRC ID 38519
Author Zhao JJ, Pan K, Li JJ, Chen YB, Chen JG, Lv L, Wang DD, Pan QZ, Chen MS, Xia JC.
Title Identification of LZAP as a new candidate tumor suppressor in hepatocellular carcinoma.
Journal PLoS ONE
Abstract BACKGROUND:LZAP was isolated as a binding protein of the Cdk5 activator p35. LZAP has been highly conserved during evolution and has been shown to function as a tumor suppressor in various cancers. This study aimed to investigate LZAP expression and its prognostic value in hepatocellular carcinoma (HCC). Meanwhile, the function of LZAP in hepatocarcinogenesis was further investigated in cell culture models and mouse models.
METHODS:Real-time quantitative PCR, western blot and immunohistochemistry were used to explore LZAP expression in HCC cell lines and primary HCC clinical specimens. The functions of LZAP in the proliferation, colony formation, cell cycle, migration, invasion and apoptosis of HCC cell lines were also analyzed by infecting cells with an adenovirus containing full-length LZAP. The effect of LZAP on tumorigenicity in nude mice was also investigated.
RESULTS:LZAP expression was significantly decreased in the tumor tissues and HCC cell lines. Clinicopathological analysis showed that LZAP expression was significantly correlated with tumor size, histopathological classification and serum α-fetoprotein (AFP). The Kaplan-Meier survival curves revealed that decreasing LZAP expression was associated with poor prognosis in HCC patients. LZAP expression was an independent prognostic marker of overall HCC patient survival in a multivariate analysis. The re-introduction of LZAP expression in the HepG2 and sk-Hep1 HCC cell lines significantly inhibited proliferation and colony formation in the HCC cells and induced G1 phase arrest and apoptosis of the HCC cells in vitro. Restoring LZAP expression in the HCC cell lines also inhibited migration and invasion. In addition, experiments with a mouse model revealed that LZAP overexpression could suppress HCC tumorigenicity in vivo.
CONCLUSIONS:Our data suggest that LZAP may play an important role in HCC progression and could be a potential molecular therapy target for HCC.
Volume 6(10)
Pages e26608
Published 2011
DOI 10.1371/journal.pone.0026608
PII PONE-D-11-08381
PMID 22028922
PMC PMC3197520
MeSH Animals Apoptosis / genetics Carcinoma, Hepatocellular / diagnosis Carcinoma, Hepatocellular / genetics Carcinoma, Hepatocellular / metabolism* Carcinoma, Hepatocellular / pathology* Cell Cycle / genetics Cell Line, Tumor Cell Movement / genetics Cell Proliferation Cell Survival / genetics Female Gene Expression Regulation, Neoplastic Humans Intracellular Signaling Peptides and Proteins / genetics Intracellular Signaling Peptides and Proteins / metabolism* Liver Neoplasms / diagnosis Liver Neoplasms / genetics Liver Neoplasms / metabolism* Liver Neoplasms / pathology* Male Mice Middle Aged Multivariate Analysis Neoplasm Invasiveness Nerve Tissue Proteins / genetics Nerve Tissue Proteins / metabolism* Prognosis Survival Analysis Tumor Suppressor Proteins / genetics Tumor Suppressor Proteins / metabolism*
IF 2.776
Times Cited 17
Human and Animal Cells