Increasing 14-3-3 Sigma Expression With Declining Estrogen Receptor Alpha and Estrogen-Responsive Finger Protein Expression Defines Malignant Progression of Endometrial Carcinoma

Pathol Int. 2005 Nov;55(11):707-15. doi: 10.1111/j.1440-1827.2005.01900.x.

Abstract

14-3-3 sigma (sigma) is a negative regulator of the cell cycle and contributes to G2 arrest. Lack of its expression due to hypermethylation of CpG islands has been reported in some carcinomas. A recent study showed that 14-3-3 sigma was down-regulated through proteolysis by estrogen-responsive finger protein (Efp). Here, we investigated the expression of 14-3-3 sigma, hormone receptors, Efp and p53 in 86 cases of endometrial adenocarcinoma and 46 cases of normal or non-neoplastic endometria by means of immunohistochemistry and methylation-specific polymerase chain reaction. In normal endometrium, 14-3-3 sigma was overexpressed in the mid- to late-secretory phase due to hypomethylation. In endometrial adenocarcinoma, 14-3-3 sigma expression was low in low grade endometrioid adenocarcinoma due to hypermethylation, and increased significantly with increasing histological grade due to hypomethylation. 14-3-3 sigma expression inversely correlated with estrogen receptor alpha, progesterone receptor and Efp, and positively correlated with myometrial invasion and lymph node metastasis. These results suggest that 14-3-3 sigma was one of the menstrual cycle-related proteins regulated by epigenetic methylation, and its expression was influenced by epigenetic methylation or hormone receptors in progression of endometrial adenocarcinoma, and therefore was more than just a cell-cycle regulator.

MeSH terms

  • 14-3-3 Proteins
  • Adenocarcinoma / immunology
  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / physiopathology
  • Adolescent
  • Adult
  • Biomarkers, Tumor / immunology
  • Biomarkers, Tumor / metabolism*
  • Cell Cycle
  • DNA-Binding Proteins / immunology
  • DNA-Binding Proteins / metabolism*
  • DNA-Binding Proteins / physiology
  • Disease Progression
  • Endometrial Neoplasms / immunology
  • Endometrial Neoplasms / metabolism*
  • Endometrial Neoplasms / physiopathology
  • Endometrium / immunology
  • Endometrium / metabolism
  • Estrogen Receptor alpha / immunology
  • Estrogen Receptor alpha / metabolism*
  • Exonucleases / immunology
  • Exonucleases / metabolism*
  • Exoribonucleases
  • Female
  • Genes, Tumor Suppressor / physiology
  • Humans
  • Immunohistochemistry
  • Lymphatic Metastasis
  • Menstrual Cycle
  • Methylation
  • Middle Aged
  • Neoplasm Proteins / immunology
  • Neoplasm Proteins / metabolism*
  • Nuclear Proteins / immunology
  • Nuclear Proteins / metabolism
  • Nuclear Proteins / physiology
  • Polymerase Chain Reaction
  • Transcription Factors / immunology
  • Transcription Factors / metabolism*
  • Tripartite Motif Proteins
  • Tumor Protein p73
  • Tumor Suppressor Proteins
  • Ubiquitin-Protein Ligases

Substances

  • 14-3-3 Proteins
  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • Estrogen Receptor alpha
  • Neoplasm Proteins
  • Nuclear Proteins
  • Transcription Factors
  • Tripartite Motif Proteins
  • Tumor Protein p73
  • Tumor Suppressor Proteins
  • TRIM25 protein, human
  • Ubiquitin-Protein Ligases
  • Exonucleases
  • Exoribonucleases
  • SFN protein, human