Inverse correlation between expression levels of p27 and the ubiquitin ligase subunit Skp2 in early esophageal squamous cell carcinoma

Anticancer Res. 2004 Mar-Apr;24(2B):777-83.

Abstract

Background: In esophageal squamous cell carcinoma (SCC), the relationship between expression of the cyclin-dependent kinase inhibitor p27 and tumor aggression and prognosis is still controversial. Moreover, the expression of S-phase kinase-interacting protein 2 (Skp2), the ubiquitin ligase subunit required for the ubiquitin-dependent degradation of p27, remains unknown.

Materials and methods: We used immunohistochemistry to analyze Skp2 and p27 expression in surgical specimens obtained from 32 patients with early esophageal SCC. We also used Western blotting to characterize the expression of Skp2 and p27 in 7 cell lines derived from esophageal SCC.

Results: Expression of Skp2 showed an inverse topographic distribution and correlation to that of p27 in many esophageal carcinomas. Of the 7 cell lines, 6 showed an inverse relationship between Skp2 and p27 expression. Patients without an inverse correlation between Skp2 and p27 expression had a significantly unfavorable prognosis in the early stage (p=0.0493).

Conclusion: These findings suggest that the target substrate of Skp2 in early esophageal SCC is mainly p27, and that failure of Skp2-induced degradation of p27 may influence tumor progression and lead to a poor prognosis.

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Squamous Cell / enzymology
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism*
  • Cell Cycle Proteins / biosynthesis*
  • Cell Cycle Proteins / genetics
  • Cell Line, Tumor
  • Cyclin-Dependent Kinase Inhibitor p27
  • Esophageal Neoplasms / enzymology
  • Esophageal Neoplasms / genetics
  • Esophageal Neoplasms / metabolism*
  • Female
  • Humans
  • Male
  • Middle Aged
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • S-Phase Kinase-Associated Proteins / biosynthesis*
  • S-Phase Kinase-Associated Proteins / genetics
  • Tumor Suppressor Proteins / biosynthesis*
  • Tumor Suppressor Proteins / genetics
  • Ubiquitin / metabolism

Substances

  • Cell Cycle Proteins
  • RNA, Messenger
  • S-Phase Kinase-Associated Proteins
  • Tumor Suppressor Proteins
  • Ubiquitin
  • Cyclin-Dependent Kinase Inhibitor p27