Premium
Alterations in the expression of the cell cycle regulatory protein cyclin kinase subunit 1 in colorectal carcinoma
Author(s) -
Shapira Ma'anit,
BenIzhak Ofer,
Bishara Bishara,
Futerman Boris,
Minkov Ira,
Krausz Michael M.,
Pagano Michele,
Hershko Dan D.
Publication year - 2004
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.20172
Subject(s) - skp2 , colorectal cancer , medicine , cancer research , immunohistochemistry , kinase , protein subunit , carcinoma , cancer , protein kinase a , ubiquitin ligase , pathology , microbiology and biotechnology , ubiquitin , biology , biochemistry , gene
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.