Downregulation of stathmin is involved in malignant phenotype reversion and cell apoptosis in esophageal squamous cell carcinoma.

Abstract

BACKGROUND AND OBJECTIVES:

Stathmin plays a critical role in the regulation of mitosis and mediates the development of malignant tumors. Here, we investigated the potential role of stathmin in cell cycle and apoptosis in esophageal squamous cell carcinoma (ESCC).

METHODS:

A stathmin short hairpin RNA (shRNA) plasmid was employed to downregulate stathmin expression in the ESCC cell line EC9706 cells. Cell proliferation was measured by cell counting, MTT, and colony formation assay. Cell migration was measured by Boyden chamber. Western blot was used to analyze the expressions of stathmin, survivin, and apoptosis-related proteins in transfected cells. Cell cycle and apoptosis were determined by flow cytometry and DNA ladder. Oncogenicity assay in nude mice was utilized to analyze phenotypic changes of transfected cells in vivo.

RESULTS:

After transfection with stathmin shRNA plasmid, stathmin expression markedly decreased in EC9706 cells. Stathmin downregulation significantly inhibited cell proliferation, cell migration in vitro, and tumorigenicity in vivo, meanwhile arrested cell cycle in the G2/M phase and induced cell apoptosis. Further, stathmin downregulation resulted in downregulation of Bcl-2 and survivin proteins, activation of Caspase-3.

CONCLUSIONS:

These findings demonstrate that stathmin may play an essential role in carcinogenesis of ESCC, which will lay a foundation for target therapy of ESCC.

• Authors: Feng Wang, Liu-Xing Wang, Sheng-Lei Li, Ke Li, Wei He, Hong-Tao Liu, Qing-Xia Fan
• Journal: Journal of surgical oncology (J Surg Oncol) Vol. 103 Issue 7 Pg. 704-15 (Jun 01 2011) ISSN: 1096-9098 [Electronic] United States
• PMID: 21360534 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Wiley-Liss, Inc.

Chemical References

• BIRC5 protein, human
• Inhibitor of Apoptosis Proteins
• Proto-Oncogene Proteins c-bcl-2
• RNA, Small Interfering
• Stathmin
• Survivin
• Caspase 3

Topics

• Animals
• Apoptosis (genetics)
• Carcinoma, Squamous Cell (metabolism, pathology)
• Caspase 3 (metabolism)
• Cell Cycle (genetics)
• Cell Line, Tumor
• Cell Movement
• Cell Proliferation
• Down-Regulation
• Esophageal Neoplasms (metabolism, pathology)
• Flow Cytometry
• Humans
• Inhibitor of Apoptosis Proteins (metabolism)
• Male
• Mice
• Mice, Nude
• Phenotype
• Plasmids
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• RNA, Small Interfering
• Stathmin (metabolism)
• Survivin
• Transfection