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
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14-3-3 Proteins
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Adenocarcinoma / immunology
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Adenocarcinoma / metabolism*
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Adenocarcinoma / physiopathology
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Adolescent
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Adult
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Biomarkers, Tumor / immunology
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Biomarkers, Tumor / metabolism*
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Cell Cycle
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DNA-Binding Proteins / immunology
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DNA-Binding Proteins / metabolism*
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DNA-Binding Proteins / physiology
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Disease Progression
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Endometrial Neoplasms / immunology
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Endometrial Neoplasms / metabolism*
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Endometrial Neoplasms / physiopathology
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Endometrium / immunology
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Endometrium / metabolism
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Estrogen Receptor alpha / immunology
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Estrogen Receptor alpha / metabolism*
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Exonucleases / immunology
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Exonucleases / metabolism*
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Exoribonucleases
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Female
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Genes, Tumor Suppressor / physiology
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Humans
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Immunohistochemistry
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Lymphatic Metastasis
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Menstrual Cycle
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Methylation
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Middle Aged
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Neoplasm Proteins / immunology
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Neoplasm Proteins / metabolism*
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Nuclear Proteins / immunology
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Nuclear Proteins / metabolism
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Nuclear Proteins / physiology
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Polymerase Chain Reaction
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Transcription Factors / immunology
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Transcription Factors / metabolism*
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Tripartite Motif Proteins
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Tumor Protein p73
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Tumor Suppressor Proteins
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Ubiquitin-Protein Ligases
Substances
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14-3-3 Proteins
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Biomarkers, Tumor
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DNA-Binding Proteins
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Estrogen Receptor alpha
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Neoplasm Proteins
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Nuclear Proteins
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Transcription Factors
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Tripartite Motif Proteins
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Tumor Protein p73
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Tumor Suppressor Proteins
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TRIM25 protein, human
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Ubiquitin-Protein Ligases
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Exonucleases
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Exoribonucleases
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SFN protein, human