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

Expression and function of the human androgen-responsive gene ADI1 in prostate cancer. Research Abstract Details 

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Expression and function of the human androgen-responsive gene ADI1 in prostate cancer. Abstract Text:

Shane W Oram,Junkui Ai,Gina M Pagani,Moira R Hitchens,Jeffrey A Stern,Scott Eggener,Michael Pins,Wuhan Xiao,Xiaoyan Cai,Riffat Haleem,Feng Jiang,Thomas C Pochapsky,Lizbeth Hedstrom,Zhou 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 formation suppression in human prostate cancer cells. Collectively, these observations argue that ADI1 may check prostate cancer progression through apoptosis and that this activity does not require metal binding.

Expression and function of the human androgen-responsive gene ADI1 in prostate cancer. Publishing Authors By Initials

SW Oram,J Ai,GM Pagani,MR Hitchens,JA Stern,S Eggener,M Pins,W Xiao,X Cai,R Haleem,F Jiang,TC Pochapsky,L Hedstrom,Z Wang,

For similar biochemical phenomena, metabolism, and nutrition: biochemical phenomena: protein binding research abstracts see: biochemical phenomena, metabolism, and nutrition: biochemical phenomena: protein binding research

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Expression and function of the human androgen-responsive gene ADI1 in prostate cancer. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Neoplasia (New York, N.Y.)

VOLUME: 9

Page Numbers: 643-51

Journal Abbreviation: Neoplasia

ISSN: 1476-5586

DAY: 3

MONTH: Aug

YEAR: 2007

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

Number of References:

LANGUAGE: eng

NlmUniqueID: 100886622

Expression and function of the human androgen-responsive gene ADI1 in prostate cancer. Keywords Mesh Terms:

KEYWORDS: Protein Binding

MESH TERMS: physiology

Chemical & Substance for Abstract: Expression and function of the human androgen-responsive gene ADI1 in prostate cancer. Information

Substance Name: Dioxygenases

Registry Number: EC 1.13.11.-

Grant and Affiliation Information for Expression and function of the human androgen-responsive gene ADI1 in prostate cancer.

AFFILIATION: Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.

Country: Canada

AGENCY: United States NIGMS

GRANT: R01 GM067786

ACRONYM: GM

MEDLINETA: Neoplasia

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