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Molecular Cancer
Published in: Molecular Cancer 1/2010

Open Access 01-12-2010 | Research

BMI1 and Mel-18 oppositely regulate carcinogenesis and progression of gastric cancer

Authors: Xiao-Wei Zhang, Ya-Ping Sheng, Qian Li, Wei Qin, You-Wei Lu, Yu-Fan Cheng, Bing-Ya Liu, Feng-Chun Zhang, Jin Li, Goberdhan P Dimri, Wei-Jian Guo

Published in: Molecular Cancer | Issue 1/2010

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Abstract

Background

The BMI1 oncogene is overexpressed in several human malignancies including gastric cancer. In addition to BMI1, mammalian cells also express Mel-18, which is closely related to BMI1. We have reported that Mel-18 functions as a potential tumor suppressor by repressing the expression of BMI1 and consequent downregulation of activated AKT in breast cancer cells. However, the mechanisms of BMI1 overexpression and the role of Mel-18 in other cancers are still not clear. The purpose of this study is to investigate the role of BMI1 and Mel-18 in gastric cancer.

Results

BMI1 was found to be overexpressed in gastric cancer cell lines and gastric tumors. Overexpression of BMI1 correlated with advanced clinical stage and lymph node metastasis; while the expression of Mel-18 negatively correlated with BMI1. BMI1 but not Mel-18 was found to be an independent prognostic factor. Downregulation of BMI1 by Mel-18 overexpression or knockdown of BMI1 expression in gastric cancer cell lines led to upregulation of p16 (p16INK4a or CDKN2A) in p16 positive cell lines and reduction of phospho-AKT in both p16-positive and p16-negative cell lines. Downregulation of BMI1 was also accompanied by decreased transformed phenotype and migration in both p16- positive and p16-negative gastric cancer cell lines.

Conclusions

In the context of gastric cancer, BMI1 acts as an oncogene and Mel-18 functions as a tumor suppressor via downregulation of BMI1. Mel-18 and BMI1 may regulate tumorigenesis, cell migration and cancer metastasis via both p16- and AKT-dependent growth regulatory pathways.
Appendix
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Metadata
Title
BMI1 and Mel-18 oppositely regulate carcinogenesis and progression of gastric cancer
Authors
Xiao-Wei Zhang
Ya-Ping Sheng
Qian Li
Wei Qin
You-Wei Lu
Yu-Fan Cheng
Bing-Ya Liu
Feng-Chun Zhang
Jin Li
Goberdhan P Dimri
Wei-Jian Guo
Publication date
01-12-2010
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2010
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/1476-4598-9-40

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