Alterations in the expression of the cell cycle regulatory protein cyclin kinase subunit 1 in colorectal carcinoma : Relation to p27Kip1 and its Ubiquitin Ligase Subunit, S Phase Kinase Protein 2
✍ Scribed by Ma'anit Shapira; Ofer Ben-Izhak; Bishara Bishara; Boris Futerman; Ira Minkov; Michael M. Krausz; Michele Pagano; Dan D. Hershko
- Publisher
- John Wiley and Sons
- Year
- 2004
- Tongue
- English
- Weight
- 250 KB
- Volume
- 100
- Category
- Article
- ISSN
- 0008-543X
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✦ Synopsis
Abstract
BACKGROUND
Low levels of p27^Kip1^ are associated with high aggressiveness and poor prognosis in various malignancies, including colorectal carcinoma. The authors showed that S phase kinase protein 2 (Skp2), the specific ubiquitin ligase subunit that targets p27^Kip1^ for degradation, was overexpressed and was inversely related to p27^Kip1^ levels in patients with colorectal carcinoma. The essential role of cyclin kinase subunit 1 (Cks1) in Skp2‐dependent p27 degradation was recently discovered, but its role in human malignancies is unknown.
METHODS
Quick‐frozen colorectal tumor samples from 30 patients were separated by electrophoresis on sodium dodecyl sulfate–polyacrylamide gels, transferred to nitrocellulose, and probed with highly specific monoclonal antibodies directed against Cks1, Skp2, and p27^Kip1^. The expression of Cks1 was also examined by immunohistochemistry using formalin‐fixed, paraffin‐embedded tissue sections from the same patients.
RESULTS
A strong correlation was found between Cks1 levels and Skp2 expression and loss of tumor differentiation. A significant inverse relation was also observed between levels of Cks1 and p27^Kip1^ and overall survival.
CONCLUSIONS
The results of the current study suggest that increased expression of Cks1 may have an important causative role in decreasing levels of p27 in patients with aggressive colorectal carcinoma. Cancer 2004. © 2004 American Cancer Society.