Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0476089 (endometrial cancer)
 11,379 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Survivin is a new member of the inhibitor of apoptosis family of anti-apoptotic proteins. It has been reported that survivin is expressed during fetal development and in cancer tissues. Because suppression of apoptosis is important for carcinogenesis and tumor growth, we investigated the expression of survivin in human endometrial carcinomas. We analyzed serial frozen sections for survivin protein expression in 31 cases of endometrial carcinoma and 20 cases of normal endometria by fluorescent immunohistochemistry. We analyzed the relationship between the percentages of survivin-stained cells and the patient's characteristics, including clinical stage, histological grade, presence of invasion to >1/2 myometrium, clinical outcome, and survival rate. Survivin was weakly detected in some normal endometria in the proliferative phase (0-5.1%) and in the secretory phase (0-15.8%). There was, however, abundant survivin immunoreactivity in the nucleus and/or cytoplasm of the endometrial carcinoma cells. Scoring on the basis of the percentage of positive cells indicated that survivin expression was significantly associated with proliferating cell nuclear antigen-labeling index, clinical stage, histological grade, the presence of invasion to >1/2 myometrium, clinical outcome, and survival rate (P<0.01, respectively). We conclude that the survivin protein is a defining diagnostic marker for endometrial carcinomas that may also yield prognostic information.
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PMID:Survivin expression correlates with clinical stage, histological grade, invasive behavior and survival rate in endometrial carcinoma. 2400 29

In a number of different cancer including endometrial cancers, tumor suppressor phosphatase tensin homologue (PTEN, a lipid phosphatase) is frequently mutated. PTEN dephosphorylates PI 3-K product, phosphatidylinositol 3,4,5-triphosphate (PIP3), into inactive PIP2 which blocks Akt activation/phosphorylation. In the present study, we have used an endometrial cancer cell line known to possess wild-type PTEN (HEC-1-A) and two mutated inactive PTEN protein cell lines (RL-95-2 and Ishikawa) to investigate importance of PI 3-K/PTEN/Akt survival pathway in endometrial cancers. As hypothesised, results showed high levels of Akt1/2 mRNAs and protein phosphorylation in the two mutated PTEN human endometrial cancer cells. To test the possible involvement of Akt in the regulation of survival factors, Bcl-2, XIAP, cIAP-1 and cIAP-2 expression were measured. cIAP-1 protein expression was high in cells expressing phospho-Akt. XIAP and cIAP-2 protein expression was not influenced by the presence of active Akt. Akt phosphorylation decreased and apoptosis was strongly increased in mutated PTEN human endometrial cancer cells in the presence of PI 3-K inhibitor (Wortmannin) which was accompanied by a down-regulation of cIAP-1 protein. Wortmannin had no effect on wild-type PTEN HEC-1-A cell line. Although, Bcl-2 expression was strongly expressed in mutated-PTEN cells, expression remained stable in the presence of Wortmannin suggesting that Bcl-2 is not regulated by Akt. Overexpression of Akt using a constitutively active Akt expression vector resulted in an up-regulation of cIAP-1 expression. These results suggest a pivotal role of Akt in the regulation of endometrial cancer cell survival through the up-regulation of a specific inhibitor of apoptosis protein.
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PMID:Akt activity in endometrial cancer cells: regulation of cell survival through cIAP-1. 1288 21

Endometrial cancer is the most common gynecological malignancy in developed countries and represents the eighth leading cause of cancer related death in women. The growing incidence of endometrial cancer leads scientists and oncologists to identify effective preventive measures and also molecular markers for diagnosis and prognosis. Chemotherapy and hormone therapy is the mainstay treatment option for advanced and recurrent endometrial cancer and response to therapy is one of the most important factor which favors prognosis and overall survival. In recent years, there have been major advances in the treatment of patients with endometrial cancer. Despite advances made in the treatment of this cancer, the overall survival of patients has not significantly improved because considerable number of patients harbor tumor refractory to these therapies and the majority of the initially responsive tumors become refractory to treatments. Therefore, determination of sensitivity/resistance is becoming increasingly important for individualization of endometrial cancer therapy. The aim of this review is to present the existing knowledge about the molecular markers that could play a crucial role in determining resistance to chemo- and hormone therapy. Extensive literature search for the cell signaling pathways and factors responsible for chemoresistance have been performed and reviewed. Several recent studies suggest that deregulations in the apoptotic pathways (such as p53, Fas/FasL, Bcl-2 family proteins, inhibitor of apoptosis proteins), survival pathways (PI3K/AKT, MAPK), hormone receptor signaling pathways (progesterone receptor), Cyclooxygenase-2 and Her-2 are considered as key factors involved in the onset and maintenance of therapeutic resistance, suggesting that resistance is a multi-factorial phenomenon.
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PMID:Resistance to chemotherapy and hormone therapy in endometrial cancer. 1919 80

The molecular progression of endometrial cancer is poorly understood, and both genetic and epigenetic factors play a role. Survivin is a member of the inhibitor of apoptosis (IAP) gene family and contains a canonical CpG island that has been described as epigenetically regulated. As survivin is overexpressed in endometrial tumors, we hypothesized that hypomethylation could explain this expression pattern. Surprisingly, methylation-specific PCR and pyrosequencing showed that survivin was hypermethylated in endometrial tumors and correlated with increased survivin expression. We speculated that methylation could inhibit the binding of p53, a repressor of survivin expression. Our data indicates that demethylation of the survivin promoter by decitabine results in p53-dependent survivin repression and that p53 binding can be inhibited by DNA methylation. We are the first to report survivin de-repression by DNA methylation. We also present microarray data, which suggest that de-repression by methylation is a general mechanism of p53 regulation. Demethylation induced by decitabine is traditionally thought to be active in tumors by allowing the re-expression of tumor suppressor genes. However, our results indicate that an additional important mechanism is to decrease the expression of oncogenes.
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PMID:DNA methylation inhibits p53-mediated survivin repression. 1936 21

Adiponectin appears to play an important role in the development and progression of several obesity-related malignancies. Also, overexpression of survivin, an inhibitor of apoptosis protein, is associated with increased risk of cancers. The aim of this study was to investigate the association between two polymorphisms in the adiponectin gene and endometrial cancer (EC) risk. We also investigated whether epistasis between surviving and adiponectin gene polymorphisms are associated with EC risk in an Iranian population. The samples comprised formalin-fixed, paraffin-embedded tissue sections obtained from the archive of the pathology department, Imam-Khomeini Hospital and Firouzgar hospital. After DNA extraction the genotyping was performed using PCR-RFLP technique. Single nucleotide polymorphisms (SNPs) in adiponectin (rs1063539, rs2241766) and survivin (rs9904341) gene were evaluated in the study. The increased frequency of ADIPOQ rs1063539C allele (CC+CG genotype) was associated with decreased EC risk [OR: 0.39(0.17-0.90)]. Survivin rs9904341C allele (CC+CG genotype) was associated with increased EC risk [crude OR: 2.75(1.27-5.95), adjusted OR: 2.93(1.27-6.76)]. We observed an epistatic interaction between survivin rs9904341 CC+CG genotype and ADIPOQ rs1063539 GG genotype increasing the risk of EC compared to those with other genotypes [OR: 4.86(1.88-12.54), P=0.001]. Our findings indicate that adiponectin might have a modulatory effect on survivin role and function in EC, which requires further investigation.
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PMID:Epistatic interaction between adiponectin and survivin gene polymorphisms in endometrial carcinoma. 2561 98