Publications by authors named "Steketee K"

We characterized the specifically androgen-regulated gene (SARG), which is expressed in the androgen receptor (AR) and glucocorticoid receptor (GR) positive cell line lymph node carcinoma of the prostate-1F5 (LNCaP-1F5). SARG mRNA expression can be up-regulated by androgens, but not by glucocorticoids. SARG mRNA expression is high in prostate tissue.

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The N-terminal domain (NTD) and the ligand-binding domain (LBD) of the androgen receptor (AR) exhibit a ligand-dependent interaction (N/C interaction). Amino acids 3-36 in the NTD (AR3-36) play a dominant role in this interaction. Previously, it has been shown that a PhixxPhiPhi motif in AR3-36, 23FxxLF27, is essential for LBD interaction.

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Article Synopsis
  • In certain prostate cancers resistant to endocrine therapy, specific amino acid substitutions (H874Y, T877A, T877S) enhance the androgen receptor's (AR) ability to bind different ligands.
  • The study involved testing these mutations in a yeast system for their responsiveness to various hormones and showed that H874Y and T877A could be activated by cortisol.
  • The results suggest that changes in the amino acids at positions 874 and 877 help the AR accept a wider range of ligands by altering the binding pocket's conformation and size.
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Androgens play a crucial role in several stages of male development and in the maintenance of the male phenotype. Androgens act in their target cells via an interaction with the androgen receptor, resulting in direct regulation of gene expression. The androgen receptor is a phosphoprotein and modulation of the phosphorylation status of the receptor influences ligand-binding and consequently transcription activation of androgen responsive genes.

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Previous studies in yeast and mammalian cells showed a functional interaction between the amino-terminal domain and the carboxy-terminal, ligand-binding domain (LBD) of the human androgen receptor (AR). In the present study, the AR subdomains involved in this in vivo interaction were determined in more detail. Cotransfection experiments in Chinese hamster ovary (CHO) cells and two-hybrid experiments in yeast revealed that two regions in the NH2-terminal domain are involved in the functional interaction with the LBD: an interacting domain at the very NH2 terminus, located between amino acid residues 3 and 36, and a second domain, essential for transactivation, located between residues 370 and 494.

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Androgen receptor-positive LNCaP cells were stably transfected with a rat glucocorticoid receptor (GR) expression plasmid. Ligand-binding studies in the generated cell lines revealed high-affinity binding of the cognate ligands to their receptors. Transfection experiments with the newly derived cell lines showed that, like androgen receptor, GR can induce activity of a prostate-specific antigen promoter fragment linked to the luciferase gene.

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The ligand binding domain (LBD) and the amino-terminal, transactivation domain (TAD) of the androgen receptor (AR) were separately linked to the GAL4 DNA binding domain (DBD) and to the GAL4(TAD). Resulting constructs were tested in the yeast two-hybrid system for protein-protein interactions. In the presence of androgen [methyltrienolone (R1881) or dihydrotestosterone (DHT)] a transcriptionally active complex was formed, reflecting an association between the AR(LBD) and the AR(TAD).

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A novel 12- and 15-lipoxygenase related gene was isolated from a mouse strain 129 genomic phage library in a screen with a human 15-lipoxygenase cDNA probe. The complete genomic sequence revealed 14 exons and 13 introns covering 7.3 kb of DNA.

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There are an estimated 4,300 cases of postoperative hemorrhage after tonsillectomy in the United States each year. Most patients seek care in the Emergency Department for this potentially fatal condition. This study was performed to characterize the clinical presentation of patients seeking Emergency Department (ED) care for posttonsillectomy and postadenoidectomy hemorrhage (PTAH).

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A cohort of 72 persons who had entered a rural Oregon county's involuntary treatment system in 1979 through 1982 was followed for six years. While schizophrenia was the most frequent diagnosis, several other conditions were represented including adjustment disorders, organic mental disorders, and substance abuse. The majority (55%) of persons with organic mental disorders died as did 12% of the individuals with schizophrenia.

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