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Published on: July 28, 2010
Alterations of Chk1 and Chk2 expression in colon cancer
Magdalena Stawinska1, Adam Cygankiewicz, Radzislaw Trzcinski
1Department of Cytobiochemistry, University of Lodz, Banacha 12/16, 90-237, Lodz, Poland.
Background And Aims:
Checkpoint kinases 1 and 2 (Chk1 and Chk2) are emerging as key mediators in diverse cellular responses to genotoxic stress, guarding the integrity of the genome. Recent studies suggest the fundamental role of Chk1 and Chk2 in the network of genome surveillance pathways which coordinate cell cycle progression with DNA repair and cell survival or death. Defects in these two serine/threonine kinases are suggested contributors to the development of both hereditary and sporadic human cancer. Little is known about physiologic activities of Chk1 and Chk2 in the colorectal cancer or their role in tumorigenesis.
Patient/Methods:
Expression of Chk1 and Chk2 and their phosphorylated, i.e., active forms (pChk1, pChk2) was examined by Western blot and ELISA analysis in colorectal carcinomas and normal colonic mucosa.
Results/Findings:
Expression of Chk2 and pChk2 was noted to be decreased in around 50% of studied cancer cases. Quantitative studies of phosphorylated Chk2 revealed significant decrease of pChk2 in early stages of colorectal carcinomas. Furthermore, tumor invasion to local lymph nodes was found to correlate with the increase of pChk2 pool in the studied cases.
Interpretation/Conclusion:
Reduced expression of Chk2 and activated Chk2 may be an important inactivating mechanism, contributing to the development of colorectal neoplasm. However, during progression of neoplasia, activated Chk2 may contribute to the invasiveness of tumor.
Insights
Reduced expression of Chk2 (checkpoint kinase 2) and its active form may contribute to colorectal cancer development. However, increased active Chk2 may promote tumor invasiveness.
Area of Science:
- Molecular Biology
- Oncology
- Cell Cycle Regulation
Background:
- Checkpoint kinases 1 and 2 (Chk1 and Chk2) are crucial for genome integrity and cellular responses to DNA damage.
- Defects in Chk1 and Chk2 are implicated in hereditary and sporadic human cancers.
- The specific roles of Chk1 and Chk2 in colorectal cancer development and tumorigenesis are not well understood.
Purpose of the Study:
- To investigate the expression and activity of Chk1 and Chk2 in colorectal cancer.
- To determine the correlation between Chk1 and Chk2 expression/activity and colorectal cancer progression.
Main Methods:
- Western blot and ELISA analysis were used to examine the expression of Chk1, Chk2, and their phosphorylated (active) forms (pChk1, pChk2).
- Analysis was performed on colorectal carcinoma tissues and adjacent normal colonic mucosa.
Main Results:
- Decreased expression of Chk2 and its active form (pChk2) was observed in approximately 50% of colorectal cancer cases.
- A significant decrease in pChk2 was noted in early-stage colorectal carcinomas.
- Increased pChk2 levels correlated with tumor invasion into local lymph nodes.
Conclusions:
- Reduced Chk2 expression and activity may be an important mechanism contributing to colorectal neoplasm development.
- Activated Chk2 might play a role in promoting tumor invasiveness during colorectal cancer progression.
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