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. 2012 Nov 21;18(43):6345-8.
doi: 10.3748/wjg.v18.i43.6345.

Is NEDD4-1 a negative regulator of phosphatase and tensin homolog in gastric carcinogenesis?

Zhen Yang, Xiao-Gang Yuan, Jiang Chen, Nong-Hua Lu

Is NEDD4-1 a negative regulator of phosphatase and tensin homolog in gastric carcinogenesis?

Zhen Yang et al. World J Gastroenterol. .

Abstract

The expression of phosphatase and tensin homolog (PTEN), a tumor suppressor gene, is frequently down-regulated in gastric carcinomas due to mutation, loss of heterozygosity, and promoter hypermethylation. However, it is unknown if additional mechanisms may account for the down-regulation of PTEN expression. While neuronal precursor cell-expressed developmentally down-regulated 4-1 (NEDD4-1) is believed to be a potential dual regulator of PTEN, there are conflicting reports regarding their interaction. To gain further insight into the role of NEDD4-1 and its association with PTEN in gastric carcinoma development, we measured the protein expression of NEDD4-1 and PTEN in gastric mucosae with various pathological lesions and found that NEDD4-1 increased from normal gastric mucosa to intestinal metaplasia and decreased from dysplasia to gastric carcinoma. These changes did not correlate with PTEN expression changes during gastric carcinogenesis. Moreover, we found similar results in protein levels in the primary tumors and adjacent non-tumorous tissues. These results differ from a previous report showing that expression of NEDD4-1 is up-regulated in gastric carcinomas, and show a more complex pattern of NEDD4-1 gene expression during gastric carcinogenesis.

Keywords: Gastric carcinogenesis; Immunohistochemistry; Neuronal precursor cell-expressed developmentally down-regulated 4-1; Phosphatase and tensin homolog.

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Figures

Figure 1
Figure 1
Immunohistochemical staining of neuronal precursor cell-expressed developmentally down-regulated 4-1 and phosphatase and tensin homolog protein in different histological samples of gastric tissues. A: The expression of neuronal precursor cell-expressed developmentally down-regulated 4-1 (NEDD4-1) in normal gastric mucosa (NGM); B: The expression of NEDD4-1 in chronic gastritis (CG); C: The expression of NEDD4-1 in intestinal metaplasia (IM); D: The expression of NEDD4-1 in dysplasia (Dys); E: The expression of NEDD4-1 in gastric carcinoma (GC); F: The expression of phosphatase and tensin homolog (PTEN) in NGM; G: The expression of PTEN in CG; H: The expression of PTEN in IM; I: The expression of PTEN in Dys; J: The expression of PTEN in GC. Magnification: × 200.
Figure 2
Figure 2
Relative neuronal precursor cell-expressed developmentally down-regulated 4-1 and phosphatase and tensin homolog protein expression level in gastric carcinoma compared to adjacent non-tumorous mucosa. Immunoblots of neuronal precursor cell-expressed developmentally down-regulated 4-1 (NEDD4-1), phosphatase and tensin homolog (PTEN) were scanned and the relative protein expression level of tumor samples vs their non-cancerous counterparts is expressed as % of β-actin. aP < 0.05.
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