The effects of HOXB7 in the promotion of migration, invasion and anti-apoptosis in gastric cancer.

Abstract

46 Background: HOX genes, a subset of the homeobox gene family, are known to be aberrantly expressed in various types of cancers. Among them, HOXB7 recently has been reported to be highly expressed in esophageal or colorectal cancers. We aimed in this study to demonstrate the critical roles of HOXB7 in development and progression of gastric cancer. Methods: We screened gene and protein expression of HOXB7 in various gastric cancer cell lines, and also compared gene expression level of HOXB7 among chronic gastritis, intestinal metaplasia and gastric cancer tissues. To figure out the oncogenic effects of HOXB7 in vitro, we performed annexin-V assay, wound closure assay and Matrigel invasion assay. We performed Western blot analysis to examine the impact of HOXB7 on AKT pathway. Results: Both mRNA and protein was substantially expressed in stomach cancer cell lines (SNU-638, SNU-719, MKN-28, MKN-45, AGS, KATO-III, NCI-N87), however, they were nearly abolished in normal gastric tissues. Gene expression was significantly higher in primary or metastatic stomach cancer, compared with chronic gastritis or intestinal metaplasia. Knockdown of HOXB7 by transfection with siRNA in AGS and SNU-638 cells significantly inhibited migration and invasion, and showed anti-apoptotic effect. Because a previous study demonstrated that enforced expression of HOXB7 could enhance PI3K/AKT pathway activity in colon cancer cells (Liao W.T. et al, Clin Cancer Res; 17(11) June 1, 2011), we investigated the modulation of AKT/PTEN pathway by HOXB7 and observed that knockdown of HOXB7 significantly downregulated phospho-AKT and upregulated PTEN in both cell lines. Furthermore, target gene products of AKT pathway including cyclin D1, survivin, Bcl-xL and MMP-9 were significantly downregulated by siHOXB7. Conclusions: Our findings suggest that HOXB7 might play a crucial role in migration, invasion and anti-apoptotic effect via modulating AKT/PTEN pathway.