title: Alterations in the expression of the cell cycle regulatory protein cyclin kinase subunit 1 in colorectal carcinoma.
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.
authors.affiliation: Department of Surgery A, Rambam Medical Center, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Ma'anit
authors.initials: M
authors.lastname: Shapira
authors.forename: Ofer
authors.initials: O
authors.lastname: Ben-Izhak
authors.forename: Bishara
authors.initials: B
authors.lastname: Bishara
authors.forename: Boris
authors.initials: B
authors.lastname: Futerman
authors.forename: Ira
authors.initials: I
authors.lastname: Minkov
authors.forename: Michael M
authors.initials: MM
authors.lastname: Krausz
authors.forename: Michele
authors.initials: M
authors.lastname: Pagano
authors.forename: Dan D
authors.initials: DD
authors.lastname: Hershko
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016203:CDC2 Protein Kinase; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology*; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D044786:S-Phase Kinase-Associated Proteins / Q000378:metabolism*; D016019:Survival Analysis; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D044786:S-Phase Kinase-Associated Proteins; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D016203:CDC2 Protein Kinase; D018844:Cyclin-Dependent Kinases