4E binding protein 1 expression is inversely correlated to the progression of gastrointestinal cancers

Several components of the eukaryotic protein synthesis apparatus have been associated with oncogenic transformation of cells. Overexpression of the initiation factor eIF4E occurs in a variety of human tumours. The aim of this study was to determine the level of expression and the phosphorylation state of eIF4E and 4E-binding protein 1 (4E-BP1) in gastrointestinal cancer, and to ascertain whether or not these factors can be used as diagnostic or prognostic markers within this type of cancer. The eIF4E levels were significantly higher in tumours compared with normal tissue (51. 5+/-4.4 vs 30.9+/-2.5 arbitrary units (A.U.)/mg of protein, p<0.001). However, phosphorylated eIF4E did not change in stomach cancers and decreased in colorectal cancers (67.1+/-1.2 vs 60.8+/-2.8%, p<0.05). 4E-BP1 expression increased in most of the gastrointestinal cancers studied. In addition, an inverse correlation between 4E-BP1 elevation and N and M stages was found, showing significant higher elevation of 4E-BP1 in Node-negative patients (11.21+/-5.74 vs 4. 03+/-2.36 n-fold, p<0.05) as well as in patients without distant metastasis (8.41+/-3.29 vs 0.97+/-0.35 n-fold, p<0.05). These results suggest that 4E-BP1 could function as a tumour suppressor. Moreover, the data show a significant dephosphorylation of 4E-BP1 in gastrointestinal tumours that correlated with an increase in the association of 4E-BP1 and eIF4E indicating a lower availability to eIF4E to recruit to the ribosomes. Our results support a possible role of 4E-BP1 as a prognostic factor in gastrointestinal carcinoma.