Overexpression of Skp2 in carcinoma of the cervix does not correlate inversely with p27 expression.
S-phase kinase associated protein 2 (Skp2) is a member of the F-box family of substrate recognition subunits of SCF-ubiquitin ligase complexes and controls progression from G(1)-S-phase by targeting cell cycle regulators such as p21 and p27. Its locus is at 5p13, a region of frequent amplification in several cancers including carcinoma of the cervix (CaCx). Overexpression of Skp2 has been observed in many cancers of an advanced stage. We examine the expression of Skp2 in 42 invasive CaCx and its correlation with tumour differentiation state and p27 expression. Using immunohistochemistry we found increased nuclear expression of Skp2 in 55% of invasive CaCx cases analysed. It is significant that poorly differentiated tumours invariably exhibit high Skp2 expression (>40% positive nuclei), whereas well-differentiated tumours express Skp2 at a lower level (<20% positive nuclei). Skp2 expression in normal cervical epithelia is <10% (positive nuclei). Increased Skp2 protein levels did not correlate inversely with p27 expression. Our data suggest that Skp2 may contribute to the progression of CaCx, however, unlike non-human papillomavirus (HPV) containing tumours, p27 is unlikely to be the major target protein contributing to malignant progression. The high prevalence of HPV types in CaCx may circumvent the need for Skp2 to eliminate p27.
Dowen
S E
SE
Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge, United Kingdom.
Scott
A
A
Mukherjee
G
G
Stanley
M A
MA
D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000096:biosynthesis*; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000378:metabolism; D004847:Epithelial Cells / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008840:Microfilament Proteins / Q000096:biosynthesis*; D009124:Muscle Proteins; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism; D044786:S-Phase Kinase-Associated Proteins; D002583:Uterine Cervical Neoplasms / Q000378:metabolism*
D018797:Cell Cycle Proteins; D008840:Microfilament Proteins; D009124:Muscle Proteins; D044786:S-Phase Kinase-Associated Proteins; C058992:Tagln protein, mouse; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)