Jun activation domain binding protein 1 expression is associated with low p27(Kip1)levels in node-negative breast cancer

Clin Cancer Res. 2003 Nov 15;9(15):5652-9.

Abstract

Purpose: The purpose is to evaluate expression levels of Jun activation domain-binding protein 1 (JAB1) in breast cancer tissue and adjacent normal tissue, to determine whether JAB1 expression is associated with p27(Kip1) expression in invasive breast carcinomas, and to evaluate the prognostic significance of JAB1 and p27(Kip1) in node-negative breast cancer.

Experimental design: JAB1 levels were measured in 10 matched pairs of invasive breast tumor tissue and adjacent normal tissue using Western blot analysis. We also investigated the immunoreactivity of JAB1 and p27(Kip1) levels in paraffin-embedded tissue specimens from 220 patients with node-negative breast cancer who had not received adjuvant systemic therapy. The median follow-up was 15 years.

Results: JAB1 was expressed at higher levels in invasive tumors than in adjacent normal tissue (P = 0.01). JAB1 overexpression was observed in 57% of invasive breast cancers. Low levels of p27(Kip1) were noted in 70% of the tumor specimens. We found an inverse correlation between JAB1 and p27(Kip1) expression levels (P = 0.01). JAB1 overexpression was associated with patient age of at least 50 years (P = 0.03) and tumor size of </=2 cm (P = 0.01). Elevated levels of p27(Kip1) were associated with low nuclear grade (P = 0.01). At 5 years of follow-up, neither JAB1 nor p27(Kip1) expression was related to disease-free survival.

Conclusions: These data indicate that JAB1 is commonly overexpressed in invasive breast carcinomas. JAB1 overexpression is associated with low levels of p27(Kip1) in node-negative breast cancer. In this study, JAB1 and p27(Kip1) were not independent prognostic factors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Breast Neoplasms / genetics*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology*
  • COP9 Signalosome Complex
  • Cell Cycle Proteins / genetics*
  • Cyclin-Dependent Kinase Inhibitor p27
  • DNA-Binding Proteins / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic / genetics*
  • Genes, Tumor Suppressor / physiology*
  • Humans
  • Immunohistochemistry
  • Intracellular Signaling Peptides and Proteins
  • Lymphatic Metastasis / genetics
  • Middle Aged
  • Peptide Hydrolases
  • Receptor, ErbB-2 / analysis
  • Receptors, Estrogen / analysis
  • Survival Analysis
  • Time Factors
  • Transcription Factors / genetics*
  • Tumor Suppressor Proteins / genetics*

Substances

  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Intracellular Signaling Peptides and Proteins
  • Receptors, Estrogen
  • Transcription Factors
  • Tumor Suppressor Proteins
  • Cyclin-Dependent Kinase Inhibitor p27
  • Receptor, ErbB-2
  • Peptide Hydrolases
  • COPS5 protein, human
  • COP9 Signalosome Complex