Background: Chromosomal instability caused by abnormal cell division is a major cause of heterogeneity which evokes highly complex and malignant features of gastric cancer. Hec1/Ndc80 is critical in regulating proper cell division at the G2/M phase. The aim of our study is to investigate the in vitro and in vivo effects of Hec1 on gastric cancer cell growth.
Methods: The mRNA levels of Hec1 in human normal and cancer tissues were analyzed using the Oncomine database. Hec1 mRNA and protein levels in human gastric cancer tissues were analyzed by quantitative realtime-PCR and immunohistochemical staining, respectively. The effects of Hec1 on cell growth were explored by Hec1 knockdown and Hec1 overexpression. Apoptosis and cell cycle distributions were analyzed by flow cytometry. In vivo tumorigenicity was performed by engrafting tumor cells into nude mice.
Results: Hec1 mRNA and protein were broadly overexpressed in many human cancers including gastric cancer. Hec1 knockdown dramatically suppressed gastric cancer cell growth in vitro and in vivo, induced apoptosis, and arrested cell division at the G2/M phase. On the contrary, Hec1 overexpression moderately promoted gastric cancer cell growth in vivo. Hec1 overexpression induced asymmetrical chromosome alignments, abnormal cell division, and thus rendered chromosomal instability.
Conclusions: Hec1 is critical in maintaining the in vitro and in vivo growth of gastric cancer cells. Elevated Hec1 levels may occur at the early stage of gastric tumorigenesis.