Zinc finger of the cerebellum (ZIC1), one of ZIC family genes, has been shown to play important roles in many cancers such as gastric cancer and breast cancer. However, there is little known about the expression and significance of ZIC1 in endometrial cancer. The aim of this study was to determine the expression pattern and clinicopathological significance of ZIC1 in endometrial cancer. The mRNA and protein expression of ZIC1 in endometrial cancer tissues was detected using the reverse-transcription polymerase chain reaction and Western blotting, respectively. Immunostaining of ZIC1 in 99 endometrial cancer samples was examined and its associations with clinicopathological parameters were analyzed. Hec-1-B cells were transfected with ZIC1-shRNA or sc-shRNA, and cell proliferation was assayed. Hec-1-B cells stably transfected with ZIC1-shRNA or sc-shRNA were subcutaneously inoculated into nude mice, and the tumor weight was measured. A significantly increased expression of ZIC1 mRNA and protein was observed in endometrial cancer tissues compared to that in normal endometrial tissues (P<0.05). Immunohistochemical analysis showed that strong cytoplasmic immunostaining of ZIC1 was observed in almost all endometrial cancer samples (90/99) while light and moderate immunostaining of ZIC1 was only detected in 17 of 30 (56.7%) normal tissues. Moreover, up-regulation of ZIC1 was significantly correlated with age, disease stage, TNM stage and FIGO stage (P<0.05). The down-regulated expression of ZIC1 contributed to the inhibition of cell proliferation, and inhibited the growth of tumor. It was concluded that ZIC1 is over-expressed in endometrial cancer tissue but not in normal tissue, and positively correlated to the malignant biological behavior of endometrial carcinogenesis.
Endometrial Neoplasms ; metabolism ; pathology ; Female ; Humans ; Middle Aged ; RNA, Messenger ; genetics ; Transcription Factors ; genetics ; metabolism

Chromosome Aberrations ; Diagnosis, Differential ; Endometrial Neoplasms ; genetics ; metabolism ; pathology ; Endometrial Stromal Tumors ; genetics ; metabolism ; pathology ; Female ; Histone Deacetylases ; metabolism ; Humans ; Immunohistochemistry ; Neprilysin ; metabolism ; Receptors, Oxytocin ; metabolism ; Repressor Proteins ; metabolism ; Sarcoma, Endometrial Stromal ; genetics ; metabolism ; pathology ; Uterine Neoplasms ; metabolism ; pathology

OBJECTIVE: To observe the expression of HELQ and RAD51C in normal endometrial and endometrial stromal sarcoma (ESS) and analyze their correlation with the clinical features of the patients. METHODS: The expressions of HELQ and RAD51C proteins were detected by immunohistochemical staining in normal endometrial tissues (14 cases) and tumor tissues from patients with ESS (37 cases) treated in Hunan Provincial Cancer Hospital from January, 2013 to December, 2016. The correlations of the expressions of the two proteins with the patients'age, FIGO staging, tissue type, tumor size, and lymph node metastasis were analyzed. RESULTS: Immunohistochemical staining showed that the expressions of HELQ and RAD51C were both decreased in ESS patients compared with the normal group, and there was a positive correlation between HELQ and RAD51C expression ( < 0.05). HELQ expression in ESS was correlated with the tumor size and type. The expressions of HELQ and RAD51C were not correlated with the patients' age, FIGO stage and status of lymph node metastasis ( > 0.05). CONCLUSIONS Homologous recombination- directed DNA repair involving HELQ and RAD51C may participate in the occurrence and progression of ESS.
DNA Helicases ; genetics ; DNA-Binding Proteins ; genetics ; Endometrial Neoplasms ; diagnosis ; physiopathology ; Endometrium ; physiopathology ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Lymphatic Metastasis ; physiopathology ; Sarcoma, Endometrial Stromal ; physiopathology

Female ; Humans ; Sarcoma, Endometrial Stromal/surgery* ; Transcription Factors/genetics* ; Endometrial Neoplasms/surgery* ; DNA-Binding Proteins ; Co-Repressor Proteins ; Repressor Proteins/genetics*

Endometrial Hyperplasia ; genetics ; pathology ; Female ; Genital Neoplasms, Female ; genetics ; pathology ; Humans ; Tandem Repeat Sequences ; Uterine Cervical Neoplasms ; etiology

BACKGROUNDEarly stage (FIGO stage I-II) endometrioid endometrial adenocarcinoma (EEA) is very common in clinical practice. However, patients with the early stage EEA show various clinical behaviors due to biological heterogeneity. Hence, we aimed to discover distinct classes of tumors based on gene expression profiling, and analyze whether the molecular classification correlated with the histopathological stages or other clinical parameters.

METHODSHierarchical clustering was performed for class discovery in 28 early stage EEA samples using a special cDNA microarray chip containing 492 genes designed for endometrial cancer. Correlations between clinicopathologic parameters and our classification were analyzed. And the significance analysis of microarrays (SAM) array was used to identify the signature genes according to the tumor grade and myometrial invasion.

RESULTSThree tumor subtypes (subtypes I, II and III) were identified by hierarchical clustering, each subtype had different clinicopathological factors, such as tumor grade, myometrial invasion status, and FIGO stage. Moreover, SAM analysis showed 34 up-regulated genes in high grade tumors, and 38 up-regulated genes and 1 down-regulated in deep myometrial invasive tumors. The overlap genes between these two high-risk factors were markedly up-regulated in subtype I, but down-regulated in subtype III.

CONCLUSIONWe have identified novel molecular subtypes in early stage EEA. Differential gene signatures characterize each tumor subtype, which could be used for recognizing the tumor risk and providing a basis for further treatment stratification.

Adenocarcinoma ; genetics ; pathology ; Endometrial Neoplasms ; genetics ; pathology ; Female ; Gene Expression Profiling ; Humans ; Neoplasm Staging ; Oligonucleotide Array Sequence Analysis

YWHAE gene is located on chromosome 17p13.3, and its product 14-3-3epsilon protein belongs to 14-3-3 protein family. As a molecular scaffold, YWHAE participates in biological processes such as cell adhesion, cell cycle regulation, signal transduction and malignant transformation, and is closely related to many diseases. Overexpression of YWHAE in breast cancer can increase the ability of proliferation, migration and invasion of breast cancer cells. In gastric cancer, YWHAE acts as a negative regulator of MYC and CDC25B, which reduces their expression and inhibits the proliferation, migration, and invasion of gastric cancer cells, and enhances YWHAE-mediated transactivation of NF-κB through CagA. In colorectal cancer, YWHAE lncRNA, as a sponge molecule of miR-323a-3p and miR-532-5p, can compete for endogenous RNA through direct interaction with miR-323a-3p and miR-532-5p, thus up-regulating K-RAS/ERK/1/2 and PI3K-AKT signaling pathways and promoting the cell cycle progression of the colorectal cancer. YWHAE not only mediates tumorigenesis as a competitive endogenous RNA, but also affects gene expression through chromosome variation. For example, the FAM22B-YWHAE fusion gene caused by t(10; 17) (q22; p13) may be associated with the development of endometrial stromal sarcoma. At the same time, the fusion transcript of YWHAE and NUTM2B/E may also lead to the occurrence of endometrial stromal sarcoma. To understand the relationship between YWHAE, NUTM2A, and NUTM2B gene rearrangement/fusion and malignant tumor, YWHAE-FAM22 fusion gene/translocation and tumor, YWHAE gene polymorphism and mental illness, as well as the relationship between 17p13.3 region change and disease occurrence. It provides new idea and basis for understanding the effect of YWHAE gene molecular mechanism and genetic variation on the disease progression, and for the targeted for the diseases.
14-3-3 Proteins/metabolism* ; Breast Neoplasms/genetics* ; Cell Line, Tumor ; Cell Proliferation/genetics* ; Cell Transformation, Neoplastic/genetics* ; Colorectal Neoplasms/genetics* ; Endometrial Neoplasms ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; MicroRNAs/genetics* ; Phosphatidylinositol 3-Kinases/metabolism* ; Sarcoma, Endometrial Stromal/pathology* ; Stomach Neoplasms/genetics* ; Transcription Factors/genetics* ; Translocation, Genetic

Adult ; Aged ; CpG Islands ; genetics ; DNA Methylation ; Endometrial Neoplasms ; genetics ; pathology ; Female ; Gene Frequency ; Genotype ; Humans ; Middle Aged ; Neoplasm Staging ; Receptor, Endothelin B ; genetics

OBJECTIVETo investigate whether PTEN can increase sensitivity of Ishikawa cells, an endometrial carcinoma cell line, to doxorubicin.

METHODSIshikawa cells transfected by PTEN gene or not were separately treated with serial concentrations of doxorubicin. The sensitivity of cells to doxorubicin was determined by MTT assay. The cells were stained with Hoechst 33258 and examined under fluorescence microscope to determine cell apoptosis. Immunoprecipitation and Western blotting analysis were performed to evaluate the effects of doxorubicin on phosphorylation of Bad and Akt/PKB.

RESULTSDoxorubicin induced cell death of the PTEN-transfected and non-transfected Ishikawa cells in a dose-dependent manner, but the cell death was more significant in PTEN-expressing clones than in parental Ishikawa cells. A low concentration of doxorubicin (0.1 micromol/L) did not affect cell apoptosis in PTEN-null Ishikawa cells, but it induced cell apoptosis in PTEN-expressing clones. A high concentration of doxorubicin (1 micromol/L) induced cell apoptosis in both cell lines. However, the percentage of apoptotic cells was higher in PTEN-expressing clones than that in parental Ishikawa cells. In the PTEN-expressing clones, expression of phospho-Akt/PKB and phospho-Bad (Ser-136) was down regulated. Doxorubicin reduced the levels of phospho-Akt/PKB and phospho-Bad (Ser-136) in both cell lines, but the most significant reduction occurred in the PTEN-expressing clones.

CONCLUSIONPTEN significantly enhances chemosensitivity of Ishikawa cells to doxorubicin. With PTEN expression, doxorubicin may exert apoptosis-induction activity by downregulation of the PI3k/Akt/PKB signaling pathway in Ishikawa cells.

Adenocarcinoma ; genetics ; pathology ; Antibiotics, Antineoplastic ; pharmacology ; Apoptosis ; drug effects ; Cell Line, Tumor ; Doxorubicin ; pharmacology ; Endometrial Neoplasms ; genetics ; pathology ; Female ; Humans ; PTEN Phosphohydrolase ; biosynthesis ; genetics ; Transfection

BACKGROUNDTumors with different gene expression develop and progress in different ways. To deepen our understanding of the progression in endometrial cancer, and provide a useful tool for accurate diagnosis and prognosis assessment, we identified the new molecular prognostic markers in endometrial carcinoma and analyzed the relationship of them with clinical and pathological features of endometrial carcinoma.

METHODSNinety-four cases of endometrial endometrioid adenocarcinoma with complete data from the Peking University People's Hospital from 2000 to 2008 and 40 cases of normal endometrium were enrolled. Among these, 30 endometrial endometrioid adenocarcinoma samples of different International Federation of Gynecology and Obstetrics (FIGO) stage were selected for further Agilent genome-wide microarray analysis. Significance analysis of microarrays (SAM) was used to identify genes that are significantly associated with tumor progress. Immunohistochemistry was utilized to identify the genes of interest in endometrial carcinoma and normal endometrium. The relationship between the genes and the age, clinical stage, histological grade, myometrium invaded depth, lymph node metastasis status, and the expression of ER, PR, P53, and PTEN were analyzed by χ(2) test.

RESULTSAnalysis between FIGO 1988 stage I and stage III identified a 362-gene "progress signature"; 171 down-regulated and 191 up-regulated genes. Among the alterative genes, TARP (T cell receptor gamma alternate reading frame protein) and KRT5 (keratin 5) decreased 3.57 fold and 5.8 fold in FIGO stage III patients. The expression of TARP in endometrial carcinoma increased compared to normal endometrium, while that of KRT5 decreased (P < 0.05). The expression of TARP and KRT5 decreased when stage, histological grading, myometrium invaded depth increased (P < 0.05). In the cases with lymph node metastasis, the expression of TARP decreased, while the expression of KRT5 did not differ (both P < 0.05) both. The expression of P53 had a negative relationship with the expression of KRT5 (P < 0.05), but not with the expression of TARP (P > 0.05). There was no correlation between the expression of TARP and KRT5 and the expression of ER, PR, PTEN (all P > 0.05). There was no significant difference in TARP and KRT5 expression in patients aged 50 or younger and patients older than 50 (P > 0.05).

CONCLUSIONThe expression of TARP and KRT5 was correlated with the progress of endometrial cancer and their role needs further study.

Adult ; Aged ; Endometrial Neoplasms ; genetics ; metabolism ; Endometrium ; metabolism ; pathology ; Female ; Humans ; Keratin-5 ; genetics ; metabolism ; Middle Aged ; Nuclear Proteins ; genetics ; metabolism