Sep 6, 2007

Expression and function of the human androgen-responsive gene ADI1 in prostate cancer

Neoplasia : an International Journal for Oncology Research
Shane OramZhou Wang


We have previously identified an androgen-responsive gene in rat prostate that shares homology with the aci-reductone dioxygenase (ARD/ARD') family of metal-binding enzymes involved in methionine salvage. We found that the gene, aci-reductone dioxygenase 1 (ADI1), was downregulated in prostate cancer cells, whereas enforced expression of rat Adi1 in these cells caused apoptosis. Here we report the characterization of human ADI1 in prostate cancer. Androgens induced ADI1 expression in human prostate cancer LNCaP cells, which was not blocked by cycloheximide, indicating that ADI1 is a primary androgen-responsive gene. In human benign prostatic hyperplasia specimens, epithelial cells expressed ADI1. Immunohistochemistry of prostate tumor tissue microarrays showed that benign regions expressed more ADI1 than tumors, suggesting a suppressive role for ADI1 in prostate cancer. Bacterial lysates containing recombinant ADI1 produced a five-fold increase in aci-reductone decay over controls, demonstrating that ADI1 has ARD activity. We generated point mutations at key residues in the metal-binding site of ADI1 to disrupt ARD function, and we found that these mutations did not affect intracellular localization, apoptosis, or colony format...Continue Reading

Mentioned in this Paper

Prostatic Neoplasms
Gene Expression Regulation, Neoplastic
Androgen Effect
Benign Prostatic Hypertrophy
Apoptosis, Intrinsic Pathway
Enzymes, antithrombotic
Squamous Transitional Epithelial Cell Count

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Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis