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Published on: June 30, 2023
Expression of beclin-1, an autophagy-related protein, in gastric and colorectal cancers
Chang Hyeok Ahn1, Eun Goo Jeong, Jong Woo Lee
1Department of Pathology, College of Medicine, The Catholic Unviersity of Korea, Seoul, Korea.
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.
Insights
Beclin-1, a key autophagy regulator, is often overexpressed in colorectal and gastric cancers, unlike in breast cancer. This suggests increased beclin-1 expression, not loss, may drive these specific tumor types.
Area of Science:
- Cell biology
- Cancer research
- Molecular oncology
Background:
- Autophagy is crucial for cell death and survival.
- Beclin-1 regulates autophagy and is implicated as a tumor suppressor.
- Loss of beclin-1 function in cancer is thought to occur via mutation or reduced expression.
Purpose of the Study:
- To investigate beclin-1 protein expression in colorectal and gastric carcinomas.
- To determine if beclin-1 expression differs between cancer tissues and normal mucosal cells.
- To explore the role of beclin-1 in colorectal and gastric tumorigenesis.
Main Methods:
- Immunohistochemistry was used to assess beclin-1 protein levels.
- Tissue microarrays of 103 colorectal and 60 gastric carcinoma samples were analyzed.
- Beclin-1 expression was correlated with clinocopathologic characteristics.
Main Results:
- Beclin-1 was expressed in 95% of colorectal and 83% of gastric carcinomas.
- Normal stomach and colon mucosa showed minimal or no beclin-1 expression.
- No significant association was found between beclin-1 expression and tumor invasion, metastasis, or stage.
Conclusions:
- Beclin-1 inactivation through loss of expression is unlikely in colorectal and gastric cancers.
- Increased beclin-1 expression in malignant cells suggests a potential role in colorectal and gastric tumor development.
- Neo-expression of beclin-1 may contribute to tumorigenesis in these cancers.
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