Increasing 14-3-3 sigma expression with declining estrogen receptor alpha and estrogen-responsive finger protein expression defines malignant progression of endometrial carcinoma.
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.
Nakayama
Hiroko
H
Department of Tumor Pathology, Gunma University, Graduate School of Medicine, Faculty of Medicine, Maebashi, Japan. hnakayam@med.gunma-u.ac.jp
Sano
Takaaki
T
Motegi
Atsushi
A
Oyama
Tetsunari
T
Nakajima
Takashi
T
D048948:14-3-3 Proteins; D000230:Adenocarcinoma / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D000293:Adolescent; D000328:Adult; D014408:Biomarkers, Tumor / Q000276:immunology / Q000378:metabolism*; D002453:Cell Cycle; D004268:DNA-Binding Proteins / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D018450:Disease Progression; D016889:Endometrial Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D004717:Endometrium / Q000276:immunology / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000276:immunology / Q000378:metabolism*; D005092:Exonucleases / Q000276:immunology / Q000378:metabolism*; D005095:Exoribonucleases; D005260:Female; D016147:Genes, Tumor Suppressor / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008597:Menstrual Cycle; D008745:Methylation; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000276:immunology / Q000378:metabolism*; D009687:Nuclear Proteins / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D016133:Polymerase Chain Reaction; D014157:Transcription Factors / Q000276:immunology / Q000378:metabolism*; D000070584:Tripartite Motif Proteins; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases
D048948:14-3-3 Proteins; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D047628:Estrogen Receptor alpha; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; D000070584:Tripartite Motif Proteins; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; C084523:TRIM25 protein, human; D044767:Ubiquitin-Protein Ligases; D005092:Exonucleases; D005095:Exoribonucleases; C413442:SFN protein, human