Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04155 (pS2)
 1,234 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this work, 52 diphenyl-4,5-dihydroisoxazoles and -3-hydroxy ketones were prepared and their estrogen receptor alpha (ERalpha) and estrogen receptor beta (ERbeta) activities were explored in order to systematize and maximize their biological activity. The biological activity was firstly screened by using ERE reporter assay to find out how aromatic hydroxylation and methylation of the chiral centers of the compounds affect the ability of ER to mediate biological responses. For selected 19 compounds, the relative binding affinities (RBA, relative to 3,17beta-estradiol) and ability to induce transcription of primary E2 target gene pS2 in human MCF-7 breast cancer cells were determined. In the reporter assay, many compounds showed even stronger activity than E2 and some of them showed RBA larger than 1%. The highest RBAs were determined for the enantiomers of 1-hydroxy-6-(4-hydroxy-phenyl)-1-phenyl-hexan-3-one (50a and 50b). Isomer 50a showed high binding affinity both to ERalpha (with RBA approximately 200%) and ERbeta (with RBA approximately 60%), while the RBAs of 50b were ca. 40% of those. Some of the other compounds (with RBA approximately 1-16%) showed also notable ERalpha binding selectivity. When four most promising ligands (50a, 50b, 45a, and 45b) were studied with respect to their ability to induce the transcription of primary E2 target gene pS2, the compounds acted as agonists or partial agonists. Computer modeling was used to predict receptor binding conformations and to rationalize the RBA differences of the compounds.
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PMID:Synthesis and biological evaluation of phenolic 4,5-dihydroisoxazoles and 3-hydroxy ketones as estrogen receptor alpha and beta agonists. 2043 Jun 32

A number of genes differentially expressed in breast cancer were isolated using a subtractive cloning technique. DNA sequence analysis and GenBank searches of T4F10, T2H7, and T2E5 cDNA clones found them to be identical with E2A, MSS1, and SEC13R genes. Their expression in a variety of primary breast tumor and cancer cell lines was compared with c-ERB-B2 and pS2 by Northern blot analysis. In breast cancer cell lines, the genes that we isolated are more frequently expressed than the previously described c-ERB-B2 and pS2.
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PMID:Identification of differentially expressed genes in breast cancer. 2154 75


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