Putative role of the mTOR/4E-BP1 signaling pathway in the carcinogenesis and progression of gastric cardiac adenocarcinoma.

ABSTRACT

The mammalian target of rapamycin/eukaryotic translation inititiation factor 4E binding protein 1 (mTOR/4E-BP1) transduction pathway is activated in a range of malignant cancers, but its role in human gastric cardiac adenocarcinoma (GCA) has not been well defined. The present study used western blotting and reverse transcription polymerase chain reaction (RT-PCR) to assess the expression of mTOR, 4E-BP1 and eukaryotic translation initiation factor 4E (eIF4E) at the protein and mRNA levels in 33 cases of GCA and paired adjacent normal gastric mucosal tissues. The expression of mTOR at the protein level in GCA was significantly lower than that in the corresponding normal gastric mucosa (0.296 ± 0.27 vs. 1.348 ± 0.80, P<0.05), but the ratio of p-mTOR to mTOR was significantly increased in tumor tissues (1.425 ± 1.07 vs. 0.450 ± 0.24, P<0.05). The expression of 4E-BP1 was significantly decreased in GCA compared with normal tissues (p<0.05), while the levels of phosphorylated 4E-BP1 (p-4E-BP1) were markedly increased in tumor tissues (p<0.05). The levels of phosphorylated eIF4E (p­eIF4E) were significantly higher in the tumors in comparison to the corresponding normal tissues (1.822 ± 0.63 vs. 0.997 ± 0.38, P<0.05), and the levels of p-eIF4E were closely correlated with lymph node metastasis (p<0.05). The mTOR/4E-BP1 signaling pathway is activated in GCA, with mTOR activated mainly through increased mTOR phosphorylation rather than protein overexpression.