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Increasing 14‐3‐3 sigma expression with declining estrogen receptor α and estrogen‐responsive finger protein expression defines malignant progression of endometrial carcinoma
Author(s) -
Nakayama Hiroko,
Sano Takaaki,
Motegi Atsushi,
Oyama Tetsunari,
Nakajima Takashi
Publication year - 2005
Publication title -
pathology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.73
H-Index - 74
eISSN - 1440-1827
pISSN - 1320-5463
DOI - 10.1111/j.1440-1827.2005.01900.x
Subject(s) - dna methylation , estrogen receptor , methylation , cancer research , biology , estrogen , epigenetics , endometrium , adenocarcinoma , progesterone receptor , estrogen receptor alpha , immunohistochemistry , medicine , endocrinology , cancer , gene expression , breast cancer , gene , biochemistry
14‐3‐3 sigma (σ) 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 σ was down‐regulated through proteolysis by estrogen‐responsive finger protein (Efp). Here, we investigated the expression of 14‐3‐3 σ, 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 σ was overexpressed in the mid‐ to late‐secretory phase due to hypomethylation. In endometrial adenocarcinoma, 14‐3‐3 σ expression was low in low grade endometrioid adenocarcinoma due to hypermethylation, and increased significantly with increasing histological grade due to hypomethylation. 14‐3‐3 σ expression inversely correlated with estrogen receptor α, progesterone receptor and Efp, and positively correlated with myometrial invasion and lymph node metastasis. These results suggest that 14‐3‐3 σ 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.