title: 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.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yan-Bin
authors.initials: YB
authors.lastname: Feng
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Shen
authors.forename: Bao-Sheng
authors.initials: BS
authors.lastname: Chen
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: Du
authors.forename: Man-Li
authors.initials: ML
authors.lastname: Luo
authors.forename: Yan
authors.initials: Y
authors.lastname: Cai
authors.forename: Ya-Ling
authors.initials: YL
authors.lastname: Han
authors.forename: Xin
authors.initials: X
authors.lastname: Xu
authors.forename: Qi-Min
authors.initials: QM
authors.lastname: Zhan
authors.forename: Ming-Rong
authors.initials: MR
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology*; D002454:Cell Differentiation; D002471:Cell Transformation, Neoplastic; D004847:Epithelial Cells / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008856:Microscopy, Fluorescence; D010641:Phenotype; D011487:Protein Conformation