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Updated: May 17, 2026
A Genetically Engineered Mouse Model of Sporadic Colorectal Cancer
Published on: July 6, 2017
Abnormal expression of GADD45B in human colorectal carcinoma
Lisha Wang1, Xiuying Xiao, Dali Li
1Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.
Background:
GADD45B is a member of the growth arrest DNA damage-inducible gene family associated with cell growth control, apoptosis, and DNA damage repair response. The aim of this study is to detect the role of GADD45B in colorectal carcinoma (CRC); the area not studied in depth to date.
Methods:
The mRNA and protein levels of GADD45B were examined by Real-Time quantitative PCR (RT-qPCR) and immunohistochemistry (IHC) in CRC tissues and adjacent noncancerous tissues (ANCT). Over-expression plasmids and SiRNA were used to regulate GADD45B expression in CRC cell lines in vitro and flow cytometry and Western blotting were used to detect apoptotic changes.
Results:
The mRNA and protein levels of GADD45B were significantly higher in CRC tissues than those in ANCT (P<0.05). Up-regulation of GADD45B was also correlated with relapse and death of CRC patients (P<0.05). The Kaplan-Meier survival curves indicated that disease-free survival (DFS) was significantly worse in CRC patients who showed GADD45B overexpression. A Cox multivariate analysis revealed that GADD45B overexpression and TNM stage were significant factors affecting patients' survival. On the other hand, as a tumor suppressor gene, GADD45B amplified from normal colorectal tissues could induce apoptosis in CRC cell lines and may be associated with the p53-mediated apoptotic pathways.
Conclusion:
GADD45B, a tumor suppressor gene potentially through the p53-mediated apoptotic pathways, is paradoxically overexpressed in CRC and as such may play an unappreciated role in tumorigenesis. The exact mechanism of GADD45B inactivation and overexpression requires further investigation. GADD45B could be a potential therapeutic target for CRC treatment in future.
Insights
Growth arrest DNA damage-inducible beta (GADD45B) is paradoxically overexpressed in colorectal cancer (CRC), correlating with poor patient survival. This gene may be a therapeutic target for CRC treatment.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- GADD45B is involved in cell growth, apoptosis, and DNA repair.
- Its role in colorectal carcinoma (CRC) has not been extensively studied.
Purpose of the Study:
- To investigate the role of GADD45B in colorectal carcinoma (CRC).
Main Methods:
- Examined GADD45B mRNA and protein levels in CRC tissues and adjacent noncancerous tissues using RT-qPCR and immunohistochemistry.
- Manipulated GADD45B expression in CRC cell lines using plasmids and SiRNA.
- Assessed apoptotic changes via flow cytometry and Western blotting.
Main Results:
- GADD45B mRNA and protein levels were significantly higher in CRC tissues compared to adjacent noncancerous tissues.
- GADD45B overexpression correlated with increased relapse and mortality in CRC patients.
- Higher GADD45B levels were associated with worse disease-free survival (DFS) and were a significant factor in patient survival, alongside TNM stage.
Conclusions:
- GADD45B is paradoxically overexpressed in CRC, acting as a tumor suppressor gene potentially via p53-mediated pathways.
- The mechanisms of GADD45B inactivation and overexpression in CRC require further research.
- GADD45B presents a potential therapeutic target for colorectal cancer treatment.
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