Abstract

BackgroundAbnormalities of cell cycle regulators are common features in human cancers, and several of these factors are associated with the early development of gastric cancers. However, recent studies have shown that gastric cancer tumorigenesis was characterized by mucin expression. Thus, expression patterns of cell cycle-related proteins were investigated in the early phase of differentiated-type gastric cancers to ascertain any mechanistic relationships with mucin phenotypes.MethodsImmunostaining for Cyclins D1, A, E, and p21, p27, p53 and β-catenin was used to examine impairments of the cell cycle in 190 gastric intramucosal differentiated-type cancers. Mucin phenotypes were determined by the expressions of MUC5AC, MUC6, MUC2 and CD10. A Ki-67 positive rate (PR) was also examined.ResultsOverexpressions of p53, cyclin D1 and cyclin A were significantly more frequent in a gastric phenotype than an intestinal phenotype. Cyclin A was overexpressed in a mixed phenotype compared with an intestinal phenotype, while p27 overexpression was more frequent in an intestinal phenotype than in a mixed phenotype. Reduction of p21 was a common feature of the gastric intramucosal differentiated-type cancers examined.ConclusionsOur results suggest that the levels of some cell cycle regulators appear to be associated with mucin phenotypes of early gastric differentiated-type cancers.

Highlights

  • Abnormalities of cell cycle regulators are common features in human cancers, and several of these factors are associated with the early development of gastric cancers

  • We studied abnormal expressions of cell cycle-related proteins that promote gastric carcinogenesis based on mucin phenotypes in gastric intramucosal differentiated-type cancers

  • Overexpression of cyclin E may primarily promote the progression of gastric cancers. These findings suggest that the high proliferation of the gastric phenotype may be characterized by the overexpression of cyclin D1 and/or cyclin A, and that the mixed phenotype is associated with cyclin A overexpression

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Summary

Introduction

Abnormalities of cell cycle regulators are common features in human cancers, and several of these factors are associated with the early development of gastric cancers. Abnormalities have been found for cyclins D1, A, E and their co-operating partners, such as cyclin-dependent kinase (cdk), that promote cell cycle progression [1,3]. These progressive factors can be inhibited by blockers, such as p21, p27 and p57, and another group of. Of the above cell cycle-related proteins, key regulators of progression through the G1 phase of the cell cycle are cyclin D1 and cyclin E, p53, p21 and p27 [1,4,6,12] Their abnormal expressions have been thought to play pivotal roles in the progression of tumorigenesis and have been found to be disturbed in a number of human malignancies. To date, its activity has not been shown to affect the pathogenesis of early differentiated-type gastric cancers

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