Alterations of Chk1 and Chk2 expression in colon cancer.
OBJECTIVE
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.


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
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.


CONCLUSIONS
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.
Stawinska
Magdalena
M
Department of Cytobiochemistry, University of Lodz, Banacha 12/16, 90-237, Lodz, Poland.
Cygankiewicz
Adam
A
Trzcinski
Radzislaw
R
Mik
Michal
M
Dziki
Adam
A
Krajewska
Wanda M
WM
D000328:Adult; D000368:Aged; D015153:Blotting, Western; D000071877:Checkpoint Kinase 1; D064447:Checkpoint Kinase 2; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000209:etiology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D010766:Phosphorylation; D011494:Protein Kinases / Q000032:analysis / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000032:analysis / Q000502:physiology*
D011494:Protein Kinases; D064447:Checkpoint Kinase 2; C000605867:CHEK1 protein, human; C578634:CHEK2 protein, human; D000071877:Checkpoint Kinase 1; D017346:Protein Serine-Threonine Kinases