Original Article
Copyright ©2013 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Dec 14, 2013; 19(46): 8619-8629
Published online Dec 14, 2013. doi: 10.3748/wjg.v19.i46.8619
P115 promotes growth of gastric cancer through interaction with macrophage migration inhibitory factor
Xiu-Jun Li, Yi Luo, Yong-Fen Yi
Xiu-Jun Li, Yong-Fen Yi, Department of Pathology, Chongqing Medical University, Chongqing 400016, China
Yi Luo, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
Author contributions: Li XJ performed the majority of experiments and wrote the manuscript; Luo Y revised the manuscript; Yi YF designed the study.
Correspondence to: Dr. Yong-Fen Yi, Department of Pathology, Chongqing Medical University, No. 1, Yixueyuan Road, Chongqing 400016, China. yiyongfen@hotmail.com
Telephone: +86-23-68485868 Fax: +86-23-68485868
Received: May 30, 2013
Revised: September 24, 2013
Accepted: September 29, 2013
Published online: December 14, 2013
Abstract

AIM: To investigate the role of P115 in the proliferation of gastric cancer cells and the mechanism involved.

METHODS: The RNA and protein level of P115 and macrophage migration inhibitory factor (MIF) in gastric cancer and normal gastric tissue/cells were measured and the effect of P115 on cell proliferation was assessed. The role of P115 in cell cycle checkpoints was investigated and the related proteins and signaling pathways, such as cyclin D1, Mcm2, p53, PCNA as well as the MAPK signaling pathway were determined. The interaction between P115 and MIF and the effect of P115 on MIF secretion were examined. The data were analyzed via one-way ANOVA comparisons between groups and P < 0.05 was considered significant.

RESULTS: P115 and MIF were both specifically expressed in gastric cancer tissues compared with normal gastric mucosa (both P < 0.01). The mRNA and protein levels of P115 and MIF in gastric cancer cell lines MKN-28 and BGC-823 were higher than in the human gastric epithelial cell line GES-1 (both P < 0.01). In MKN-28 and BGC-823 cell lines, P115 promoted cell proliferation and G0-G1 to S phase transition. In addition, several cell cycle-related regulators, including cyclin D1, Mcm2, PCNA, pERK1/2 and p53 were up-regulated by P115. Furthermore, the interaction between P115 and MIF was confirmed by co-immunoprecipitation assay. ELISA showed that P115 stimulated the secretion of MIF into the culture supernatant (P < 0.01) and the compensative expression of MIF in cells was observed by Western blotting.

CONCLUSION: P115 promotes proliferation of gastric cancer cells through an interaction with MIF.

Keywords: Gastric cancer, P115, Migration inhibitory factor, Proliferation, Protein interaction

Core tip: Gastric cancer is one of the most common cancers. P115 is a tether protein which plays a key role in cell proliferation through combination with binding partners, including migration inhibitory factor (MIF). The present study showed that P115 and MIF were specifically expressed in gastric cancer tissues and cells. P115 promoted cell proliferation and G0-G1 to S phase transition. Cell cycle regulators, including cyclin D1, Mcm2, PCNA, pERK1/2 and p53 were up-regulated by P115. P115 interacted with MIF and stimulated the secretion of MIF into the culture supernatant. In summary, P115 promotes proliferation of gastric cancer cells through an interaction with MIF.