Ataxin-3 expression correlates with the clinicopathologic features of gastric cancer

Abstract

To investigate the expression of Ataxin-3 in human gastric cancer tissues and cell lines, and explore its clinical pathologic significance.

Methods: The expression of Ataxin-3 in gastric cancer (n=536) and noncancerous gastric mucosa (n=312) was determined by immunohistochemistry and correlated to clinicopathologic features such as histologic differentiation and tumor size. The expression of Ataxin-3 protein in the human gastric cancer cell lines MKN45, SGC7901 and in normal human gastric epithelial cells (GES-1) was also evaluated by Western blot analysis. Quantitative real-time PCR was used to determine Ataxin-3 mRNA expression in human gastric cancer cell lines and tissues.

Results: The expression of Ataxin-3 protein was decreased in the gastric cancer compared to noncancerous gastric tissue, and correlated with tumor size, Lauren classification, histologic differentiation, and mutant p53 protein (P < 0.05). Similarly, Ataxin-3 mRNA expression was decreased in the gastric cancers compared to the noncancerous gastric tissue. Ataxin-3 protein and mRNA expression was lower in MKN45, SGC7901 cells than in the normal GES-1 cells.

Conclusion: Decreased expression of Ataxin-3 may play an important role in gastric carcinogenesis and development of gastric cancer.

Keywords: Ataxin-3; clinicopathologic features; gastric cancer.

Figure 1

Expression of Ataxin-3 protein in human gastric cancer and noncancerous tissues. A: Representative tissue section showing moderate immunoreactivity (++) in GC tissue. B: An example of weak immunoreactivity (+) in GC tissue. C: An example of a GC tumor with negative immunoreactivity (-). D: Noncancerous gastric mucosa exhibiting strong Ataxin-3 immunoreactivity (+++). (All slides ×200 magnification).

Figure 2

Western blot analysis of Ataxin-3 protein expression in human GC cell lines (MKN45 and SGC7901) and human normal gastric epithelial cells (GES-1). Ataxin-3 protein expression was highest in the GES-1 cells and higher in SGC7901 than MKN45.

Figure 3

Quantitative RT-PCR analysis of Ataxin-3 mRNA expression. Ataxin-3 mRNA expression was lower in gastric cancer tissues and gastric cancer cell lines than in the control noncancerous gastric tissues and cell line. A: Expression of Ataxin-3 mRNA in human tissue samples (GC - n = 14; noncancerous gastric mucosa - n = 14; Standard Error of the Mean (SEM), experiment performed in triplicate; Ataxin-3 mRNA expression relative to GAPDH). B: Expression of Ataxin-3 mRNA in human GC cell lines (MKN45 and SGC7901) and in normal gastric epithelial cells (GES-1).