Exogenous expression of Esophagin/SPRR3 attenuates the tumorigenicity of esophageal squamous cell carcinoma cells via promoting apoptosis.

Abstract

Esophagin/SPRR3 is one of the cornified-envelope structural precursor proteins, which is expressed during epithelia cell differentiation. In 1996, another research group discovered, and our own laboratory subsequently confirmed, frequent and dramatic decreased Esophagin/SPRR3 expression in esophageal squamous cell carcinoma (ESCC). However, the role of Esophagin/SPRR3 in tumorigenesis of esophageal epithelium remains undetermined. In this study, we demonstrate that expression of Esophagin/SPRR3 is frequently downregulated in ESCC. In contrast, no correlations between downregulation of Esophagin/SPRR3 expression and clinicopathologic characteristics were observed. Diminished Esophagin/SPRR3 expression was present in dysplastic epithelia, suggesting that Esophagin/SPRR3 alteration could represent an early event in squamous carcinogenesis of the esophagus. Exogenous expression of Esophagin/SPRR3 significantly suppressed the ability of ESCC cells to form colonies in plastic and soft agar, as well as tumor formation in vivo. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end label assay and immunofluorescence analysis of the active form of Caspase 3 indicated that dysregulated apoptosis might contribute to reduced tumorigenicity. In particular, upregulation of CDK11p46 protein was observed in ESCC cells expressing Esophagin/SPRR3, but not in control cells, indicating that Esophagin/SPRR3-induced apoptosis may be due, at least in part, to increased expression of CDK11p46 protein. These findings suggest that Esophagin/SPRR3 may play a role in the maintenance of normal esophageal epithelial homeostasis, and that aberrant expression of Esophagin/SPRR3 may contribute to the tumorigenesis of ESCC.

• Authors: Yu Zhang, Yan-Bin Feng, Xiao-Ming Shen, Bao-Sheng Chen, Xiao-Li Du, Man-Li Luo, Yan Cai, Ya-Ling Han, Xin Xu, Qi-Min Zhan, Ming-Rong Wang
• Journal: International journal of cancer (Int J Cancer) Vol. 122 Issue 2 Pg. 260-6 (Jan 15 2008) ISSN: 1097-0215 [Electronic] United States
• PMID: 17935133 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2007 Wiley-Liss, Inc.

Topics

• Animals
• Apoptosis
• Carcinoma, Squamous Cell (metabolism, pathology)
• Cell Differentiation
• Cell Transformation, Neoplastic
• Epithelial Cells (metabolism)
• Esophageal Neoplasms (metabolism, pathology)
• Gene Expression Regulation, Neoplastic
• Humans
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Microscopy, Fluorescence
• Phenotype
• Protein Conformation