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)

We have studied by immunocytochemistry and monoclonal antibodies the presence and localization of estrogen receptors, progesterone receptors, and a 24-kD estrogen-regulated heat shock protein in biopsies from breast and endometrial cancer patients. Three different tissue processing protocols were used to colocalize the antigens in the same tissue sections: a) frozen sections, b) formalin fixation with routine paraffin embedding, and c) picric acid-formaldehyde (PAF) fixation with a rapid embedding in paraffin. Frozen sections showed good receptor staining but poor 24-kD protein immunoreactivity, while routine paraffin sections (with or without DNase pretreatment) were inadequate to reveal the nuclear receptor proteins at the same level seen in frozen sections. On the other hand, all three proteins could be detected satisfactorily in PAF-fixed paraffin-embedded tissue. Using this procedure we were able to visualize 24-kD protein and estrogen receptor or progesterone receptor in individual cells in paraffin sections. The study revealed that in all of the estrogen receptor positive breast and endometrial tumor samples, almost 90% of the cells expressing the cytoplasmic 24-kD protein contained estrogen receptor in the cell nucleus. In contrast, 24-kD immunoreactive cells did not express progesterone receptors in almost 40% of the progesterone receptor positive tumor samples.
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PMID:Colocalization of estrogen and progesterone receptors with an estrogen-regulated heat shock protein in paraffin sections of human breast and endometrial cancer tissue. 208 75

Effects of prostaglandin F2 alpha, E2, D2 and J2 on the DNA and RNA contents of a human endometrial cancer cell lines (SNG and Ishikawa) were studied using flow cytometry. Cytotoxic effects of various prostaglandins on SNG and Ishikawa cell lines were examined and PG J2 and PG D2 were found most active. Among other prostaglandins PG E2 showed a comparable inhibitory activity to cellular growth but PG F2 alpha didn't. In SNG and Ishikawa cell lines after RNase treatment, PG J2, PG D2 and PG E2 caused a decrease of the S-phase and G2 + M-phase cell population in cell cycle. On the other hand, PG F2 alpha caused a increase of the S-phase cell population in cell cycle PG J2, PG D2 and PG E2 after DNase treatment caused a decrease of the relative RNA content in both of cell lines. On the other hand, PG F2 alpha caused a increase of the relative RNA content. It is a noteworthy that PG J2 and PG D2 were remarkably recognized delay of doubling time and decrease of survival fraction under the time and dose dependence. These effects occur not only by direct lethal influence of the prostaglandins, but also by substantially inhibit RNA and DNA synthesis with a delay of the cell cycle. These results might be suggested a role for prostaglandin J2 and D2 in the regulation of growth of endometrial adenocarcinoma cells.
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PMID:[Inhibition of growth of human endometrial adenocarcinoma cells in vitro treated with prostaglandin F2 alpha, E2, D2 and J2]. 346 9

Genome-wide association studies (GWASs) have discovered numerous single nucleotide polymorphisms (SNPs) associated with human complex disorders. However, functional characterization of the disease-associated SNPs remains a formidable challenge. Here we explored regulatory mechanism of a SNP on chromosome 9p21 associated with endometriosis by leveraging "allele-specific" functional genomic approaches. By re-sequencing 1.29 Mb of 9p21 region and scrutinizing DNase-seq data from the ENCODE project, we prioritized rs17761446 as a candidate functional variant that was in perfect linkage disequilibrium with the original GWAS SNP (rs10965235) and located on DNase I hypersensitive site. Chromosome conformation capture followed by high-throughput sequencing revealed that the protective G allele of rs17761446 exerted stronger chromatin interaction with ANRIL promoter. We demonstrated that the protective allele exhibited preferential binding affinities to TCF7L2 and EP300 by bioinformatics and chromatin immunoprecipitation (ChIP) analyses. ChIP assays for histone H3 lysine 27 acetylation and RNA polymerase II reinforced the enhancer activity of the SNP site. The allele specific expression analysis for eutopic endometrial tissues and endometrial carcinoma cell lines showed that rs17761446 was a cis-regulatory variant where G allele was associated with increased ANRIL expression. Our work illuminates the allelic imbalances in a series of transcriptional regulation from factor binding to gene expression mediated by chromatin interaction underlie the molecular mechanism of 9p21 endometriosis risk locus. Functional genomics on common disease will unlock functional aspect of genotype-phenotype correlations in the post-GWAS stage.
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PMID:Allelic Imbalance in Regulation of ANRIL through Chromatin Interaction at 9p21 Endometriosis Risk Locus. 2705 16