Expression of beclin-1, an autophagy-related protein, in gastric and colorectal cancers

Abstract

Autophagy plays important roles in both cell death and cell survival. Beclin-1, a key regulator of autophagy formation, has been considered as a haploinsufficient tumor suppressor. Loss of expression or point mutation could serve as a mechanism of loss of beclin-1 tumor suppressor function in cancers. However, our recent study revealed that point mutation of the beclin-1 gene is a rare event in common human cancers. In this study we investigated beclin-1 protein expression in 103 colorectal and 60 gastric carcinoma tissues by immunohistochemistry using a tissue microarray approach. In the cancers, expression of beclin-1 was detected in 95% of the colorectal carcinomas and 83% of the gastric carcinomas. In contrast, normal mucosal cells of both stomach and colon showed no or very weak expression of beclin-1. There was no significant association of beclin-1 expression with clinocopathologic characteristics, including invasion, metastasis and stage. The beclin-1 expression of colorectal and gastric cancers in the present study is quite in contrast to that of the breast cancers in the previous study, which showed a decreased beclin-1 expression in breast cancer cells compared to normal breast cells. Our data indicate that beclin-1 inactivation by loss of expression may not occur in colorectal and gastric cancers. Rather, increased expression of beclin-1 in the malignant colorectal and gastric epithelial cells compared to their normal mucosal epithelial cells suggests that neo-expression of beclin-1 may play a role in both colorectal and gastric tumorigenesis.