Related Experiment Videos
Histone acetylation and gastrointestinal carcinogenesis
Wataru Yasui1, Naohide Oue, Shigehiro Ono
1Department of Molecular Pathology, Hiroshima University Graduate School of Biomedical Sciences, Kasumi, Minami-ku, Hiroshima 734-8551, Japan. wyasui@hiroshima-u.ac.jp
Annals of the New York Academy of Sciences
|May 2, 2003
Summary
Altered histone acetylation is crucial in gastrointestinal cancer progression, invasion, and metastasis. Targeting histone acetylation offers a promising therapeutic strategy for preventing and treating advanced cancers.
Area of Science:
- Epigenetics
- Cancer Biology
- Molecular Oncology
Background:
- Histone acetylation and chromatin remodeling are key epigenetic regulators of gene expression.
- Imbalances in histone acetyltransferases and deacetylases disrupt nucleosome structure, affecting DNA accessibility.
- Reduced global histone acetylation, particularly acetylated histone H4, is observed in gastric and colorectal cancers.
Purpose of the Study:
- To investigate the role of altered histone acetylation in gastrointestinal carcinogenesis, focusing on invasion and metastasis.
- To explore the therapeutic potential of targeting histone acetylation in cancer treatment.
Main Methods:
- Analysis of histone acetylation levels in tumor cells.
- Correlation of histone acetylation with tumor invasion and metastasis.
- Treatment with histone deacetylase inhibitor (trichostatin A - TSA).
- Serial analysis of gene expression (SAGE) to identify novel metastasis suppressors.
Main Results:
- Reduced histone acetylation correlates significantly with increased tumor invasion depth and lymph node metastasis in gastrointestinal cancers.
- TSA treatment increases histone acetylation, suppresses cancer cell invasion, and induces apoptosis.
- TSA upregulates expression of metastasis suppressors like tissue inhibitors of metalloproteinase and nm23H1/H2.
- SAGE identified a novel candidate metastasis suppressor gene induced by histone acetylation.
Conclusions:
- Histone deacetylation contributes to tumorigenesis, invasion, and metastasis in gastrointestinal cancers.
- Histone acetylation represents a promising therapeutic target for invasive and metastatic cancers.
- Targeting histone acetylation may also play a role in cancer prevention strategies.